20 results on '"A Arias M"'
Search Results
2. Topiramate increases the rewarding properties of cocaine in young-adult mice limiting its clinical usefulness
- Author
-
Arenas, M. C., Mateos-García, A., Manzanedo, C., Rodríguez-Arias, M., Aguilar, M. A., Navarrete, F., Gutiérrez, M. S. García, Manzanares, J., and Miñarro, J.
- Published
- 2016
- Full Text
- View/download PDF
3. Sex differences in the long-lasting consequences of adolescent ethanol exposure for the rewarding effects of cocaine in mice
- Author
-
Mateos-García, A, Manzanedo, C, Rodríguez-Arias, M, Aguilar, M. A., Reig-Sanchis, E., Navarro-Francés, C. I., Valverde, O., Miñarro, J., and Arenas, M. C.
- Published
- 2015
- Full Text
- View/download PDF
4. Higher sensitivity to the conditioned rewarding effects of cocaine and MDMA in High-Novelty-Seekers mice exposed to a cocaine binge during adolescence
- Author
-
Mateos-García, A., Roger-Sánchez, C., Rodriguez-Arias, M., Miñarro, J., Aguilar, M. A., Manzanedo, C., and Arenas, M. C.
- Published
- 2015
- Full Text
- View/download PDF
5. Cannabidiol Modulates Behavioural and Gene Expression Alterations Induced by Spontaneous Cocaine Withdrawal
- Author
-
Gasparyan A, Navarrete F, Rodriguez-Arias M, Minarro J, and Manzanares J
- Subjects
cannabidiol ,mice ,Cocaine ,withdrawal ,mRNA - Abstract
The aim of this study was to evaluate the effects of cannabidiol (CBD) on the behavioural and gene expression changes in a new animal model of spontaneous cocaine withdrawal. For this purpose, male CD-1 mice were exposed to progressive increasing doses of cocaine for 12 days (15 to 60 mg/kg/day, i.p.), evaluating spontaneous cocaine withdrawal 6 h after the last cocaine administration. The effects of CBD (10, 20, and 40 mg/kg, i.p.) were evaluated on cocaine withdrawal-induced alterations in motor activity, somatic signs, and anxiety-like behaviour. Furthermore, gene expression changes in dopamine transporter (DAT) and tyrosine hydroxylase (TH) in the ventral tegmental area, and in cannabinoid receptors 1 (CNR1) and 2 (CNR2) in the nucleus accumbens, were analysed by real-time PCR. The results obtained in the study showed that mice exposed to the spontaneous cocaine withdrawal model presented increased motor activity, somatic withdrawal signs, and high anxiety-like behaviour. Interestingly, the administration of CBD normalized motor and somatic signs disturbances and induced an anxiolytic effect. Moreover, the administration of CBD blocked the increase of DAT and TH gene expression in mice exposed to the cocaine withdrawal, regulated the decrease of CNR1 and induced an additional upregulation of CNR2 gene expression. Thus, this model of spontaneous cocaine withdrawal induces clear behavioural and gene expression changes in mice. Interestingly, CBD alleviates these behavioural and gene expression alterations suggesting its potential for the management of cocaine withdrawal.
- Published
- 2021
6. Changes in gene expression and sensitivity of cocaine reward produced by a continuous fat diet
- Author
-
Blanco-Gandía MC, Aracil-Fernández A, Montagud-Romero S, Aguilar MA, Manzanares J, Miñarro J, and Rodríguez-Arias M
- Subjects
High-fat diet ,Mu-opioid receptor ,nervous system ,Cocaine ,digestive, oral, and skin physiology ,food and beverages ,CB1 ,psychological phenomena and processes ,Conditioned place preference - Abstract
RATIONALE: Preclinical studies report that free access to a high-fat diet (HFD) alters the response to psychostimulants. OBJECTIVES: The aim of the present study was to examine how HFD exposure during adolescence modifies cocaine effects. Gene expression of CB1 and mu-opioid receptors (MOr) in the nucleus accumbens (N Acc) and prefrontal cortex (PFC) and ghrelin receptor (GHSR) in the ventral tegmental area (VTA) were assessed. METHODS: Mice were allowed continuous access to fat from PND 29, and the locomotor (10 mg/kg) and reinforcing effects of cocaine (1 and 6 mg/kg) on conditioned place preference (CPP) were evaluated on PND 69. Another group of mice was exposed to a standard diet until the day of post-conditioning, on which free access to the HFD began. RESULTS: HFD induced an increase of MOr gene expression in the N Acc, but decreased CB1 receptor in the N Acc and PFC. After fat withdrawal, the reduction of CB1 receptor in the N Acc was maintained. Gene expression of GHSR in the VTA decreased during the HFD and increased after withdrawal. Following fat discontinuation, mice exhibited increased anxiety, augmented locomotor response to cocaine, and developed CPP for 1 mg/kg cocaine. HFD reduced the number of sessions required to extinguish the preference and decreased sensitivity to drug priming-induced reinstatement. CONCLUSION: Our results suggest that consumption of a HFD during adolescence induces neurobiochemical changes that increased sensitivity to cocaine when fat is withdrawn, acting as an alternative reward.
- Published
- 2017
7. Effects of bingeing on fat during adolescence on the reinforcing effects of cocaine in adult male mice
- Author
-
Blanco-Gandía MC, Cantacorps L, Aracil-Fernández A, Montagud-Romero S, Aguilar MA, Manzanares J, Valverde O, Miñarro J, and Rodríguez-Arias M
- Subjects
Binge eating ,Conditioned place preference ,digestive, oral, and skin physiology ,Gene expression ,Self-administration ,Cocaine ,Fat - Abstract
Binge eating is a specific form of overeating characterized by intermittent excessive eating. In addition to altering the neurobiological reward system, several studies have highlighted that consumption of palatable food increases vulnerability to drug use. The aim of the present study was to evaluate the effects of a high-fat diet consumed in a binge pattern during adolescence on the reinforcing effects of cocaine. After 40 days of binge-eating for 2 h, three days a week (PND 29-69), the reinforcing effects of cocaine on conditioning place preference and intravenous self-administration paradigm were evaluated in adolescent male mice. Circulating leptin and ghrelin levels and the effects of bingeing on fat on CB1 mu opioid receptor (MOr) and ghrelin receptor (GHSR) gene expression in the Nucleus Accumbens (NAcc) and Ventral Tegmental Area (VTA) were also assessed. Our results showed a significant escalation in the consumption of a high-fat diet between the first and last week. High-fat binge (HFB) animals were more sensitive to the reinforcing effects of a subthreshold dose of cocaine in the paradigms assayed, and animals under fat withdrawal were more vulnerable to the reinstatement of conditioned place preference. HFB mice also showed enhanced cocaine self-administration. After fat withdrawal, exposure to a new fat binge reinstated cocaine seeking. Although HFB did not modify leptin levels, a decrease in plasmatic ghrelin was observed. Moreover, this pattern of fatty diet resulted in a reduction of MOr and CB1 gene expression in the NAcc and an increase in GHSR expression in the VTA. We propose that bingeing on fat during adolescence induces long-lasting changes in the brain through the sensitization of brain reward circuits, which predisposes individuals to seek cocaine during adulthood.
- Published
- 2017
8. Acute behavioural and neurotoxic effects of MDMA plus cocaine in adolescent mice
- Author
-
Daza-Losada, M., Rodríguez-Arias, M., Maldonado, C., Aguilar, M.A., Guerri, C., and Miñarro, J.
- Subjects
- *
ECSTASY (Drug) , *COCAINE , *NEUROTOXICOLOGY , *MICE behavior , *LABORATORY mice , *HYPERKINESIA , *TRANQUILIZING drugs , *BRAIN physiology , *SEROTONIN - Abstract
Abstract: The poly-drug pattern is the most common among those observed in MDMA users, with cocaine being a frequently associated drug. This study evaluates the acute effects of MDMA (5, 10 and 20 mg/kg), alone or in combination with cocaine (25 mg/kg), on motor activity, anxiety (elevated plus maze and social interaction test), memory and brain monoamines in adolescent mice. Both drugs, administered alone or concurrently, produced hyperactivity and a decrease in social contacts. However, an anxiolytic effect, studied by means of the elevated plus maze and expressed as an increase in the time spent on the open arms, was observed only in those animals treated with cocaine and MDMA. The passive avoidance task was affected only with the highest MDMA dose (20 mg/kg). Mice treated with MDMA did not present significant changes in brain monoamines, while those receiving MDMA and cocaine showed a decrease in DA in the striatum, which was accompanied by an increase in the serotonin concentration in the striatum and cortex 30 min after acute administration. In conclusion, the combined use of MDMA and cocaine produces a predominance of serotonin over DA, which is associated with an anxiolytic profile, defensive behaviours and fewer social contacts. [Copyright &y& Elsevier]
- Published
- 2009
- Full Text
- View/download PDF
9. Behavioural and neurotoxic long-lasting effects of MDMA plus cocaine in adolescent mice
- Author
-
Daza-Losada, M., Rodríguez-Arias, M., Maldonado, C., Aguilar, M.A., and Miñarro, J.
- Subjects
- *
ECSTASY (Drug) , *COCAINE , *LABORATORY mice , *DOPAMINE , *TRANQUILIZING drugs , *SEROTONIN , *PHYSIOLOGY - Abstract
Abstract: The poly-drug pattern is the most common among MDMA users, with cocaine being a frequently associated drug. The aim of the present work was to evaluate the behavioural and neurotoxic long-term effects of exposure during adolescence to MDMA alone or plus cocaine. Mice of 28 to 30 days of age received a treatment of two daily injections of an identical dose of MDMA (5, 10 or 20 mg/kg), alone or plus cocaine (25 mg/kg), for 3 days (6 administrations). Three weeks after receiving MDMA, an increase in the time dedicated by the animals to social contacts with their conspecifics was observed, whilst their behaviour in the elevated plus maze showed no differences from that of non-treated mice. After being exposed to MDMA plus cocaine, mice spent more time in social contacts during the interaction test, as well as exhibiting an anxiolytic profile in the elevated plus maze, with an increase in the time and number of entries in the open arms. The activity of mice treated with cocaine alone or plus MDMA remained constant; the decrease observed among the rest of the animals after the second hour was absent in their case. The level of dopamine in the striatum was diminished in mice treated with 20 mg/kg of MDMA, but this neurotransmitter was not affected in animals exposed to the same dose plus cocaine. The present results highlight pronounced alterations in the behaviour of adult mice after exposure to MDMA and cocaine during adolescence, and demonstrate that these long-term effects can occur without the dopaminergic system becoming affected. [Copyright &y& Elsevier]
- Published
- 2008
- Full Text
- View/download PDF
10. Effect of adolescent exposure to MDMA and cocaine on acquisition and reinstatement of morphine-induce CPP
- Author
-
Daza-Losada, M., Rodríguez-Arias, M., Aguilar, M.A., and Miñarro, J.
- Subjects
- *
NARCOTICS , *DRUGS , *CENTRAL nervous system depressants , *DRUGS of abuse - Abstract
Abstract: It is well known that an elevated percentage of ecstasy users also consume cocaine. Recently, it has been reported that a high frequency of heroin smokers first consumed heroin under the effects of ecstasy with the hope of reducing the stimulant effects of the latter drug. The aim of the present study was to evaluate the effect of exposure to MDMA and cocaine during adolescence on morphine-induced conditioned place preference (CPP) and reinstatement in adulthood. In the first experiment, adolescent mice were exposed to six injections of MDMA and three weeks later their response to the reinforcing properties of 40 mg/kg of morphine was evaluated using the CPP paradigm. All the treatment groups developed the same magnitude of morphine-induced preference and, after CPP was extinguished, it was restored in all the groups with a priming dose of 10 mg/kg of morphine. Only mice that had been treated with 10 or 20 mg/kg of MDMA had their morphine-induced preference reinstated after receiving only 5 mg/kg of morphine. In the second experiment, adolescent mice were similarly treated with six administrations of cocaine (25 mg/kg) or cocaine plus MDMA (5, 10 or 20 mg/kg), and their response to morphine-induce CPP was evaluated three weeks later. Similarly to the first experiment, all the groups developed a preference for the morphine-paired compartment, but this preference was not reinstated with a priming dose of 10 mg/kg of morphine following extinction, as was the case among the control animals. These results lead us to hypothesize that periadolescent MDMA exposure alters responsiveness to the rewarding properties of morphine, highlighting MDMA as a gateway drug whose use may increase the likelihood of dependence on other drugs. [Copyright &y& Elsevier]
- Published
- 2008
- Full Text
- View/download PDF
11. Effect of memantine and CNQX in the acquisition, expression and reinstatement of cocaine-induced conditioned place preference
- Author
-
Maldonado, C., Rodríguez-Arias, M., Castillo, A., Aguilar, M.A., and Miñarro, J.
- Subjects
- *
METHYL aspartate , *COCAINE , *GLUTAMIC acid , *NEURAL transmission - Abstract
Abstract: The present study evaluates the effect of memantine, a non-competitive N-methyl-d-aspartate (NMDA) glutamate receptor antagonist and CNQX, an alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA)/kainate receptor antagonist on the rewarding effects of cocaine in mice, using the conditioned place preference (CPP) paradigm. Cocaine-induced CPP was studied pairing this drug with different memantine or CNQX doses during either the acquisition or the expression phase of the procedure. Once CPP was established, and the preference extinguished, reinstatement was induced by a priming dose of cocaine. Both antagonists, which in themselves do not present motivational actions on the preference shown by the animals, abolished the acquisition and expression of the cocaine-induced CPP. Neither of the antagonists precipitated reinstatement of the preference induced by cocaine but memantine blocked the cocaine-primed reinstatement. Our results suggest that cocaine-induced CPP and reinstatement is largely dependent on glutamate neurotransmission, and confer a putative role for memantine among the tools useful for cocaine management and treatment. [Copyright &y& Elsevier]
- Published
- 2007
- Full Text
- View/download PDF
12. Prenatal cocaine exposure alters spontaneous and cocaine-induced motor and social behaviors
- Author
-
Estelles, J., Rodríguez-Arias, M., Maldonado, C., Aguilar, M.A., and Miñarro, J.
- Subjects
- *
COCAINE , *SUBSTANCE abuse in pregnancy , *DRUG abuse , *PREGNANCY - Abstract
Abstract: The abuse of cocaine in pregnant women could affect emotional behaviors in their descendents. The aim of this work was to evaluate the effects of prenatal cocaine exposure on spontaneous and cocaine-induced motor and social behaviors in mice. Three kinds of prenatal treatment were used: non-treated animals; mice treated daily with physiological saline during the last week of pregnancy; and finally, those treated with cocaine (25 mg/kg) during the same period. Behavioral studies took place on adult males, which were housed in two different conditions: grouped (non-aggressive), or isolated (aggressive). Cocaine-pretreated animals exhibited slight differences in spontaneous motor activity, but alterations in their social relationship with conspecifics were presented, with decreases in isolated but increases in grouped mice. The cocaine challenge increased aggression specifically in grouped prenatally cocaine-treated mice, but increases in motor activity or avoidance and flee behavior were presented in those animals pretreated with either saline or cocaine. Isolated saline-or cocaine-treated animals exhibited greater concentrations of DA and DOPAC than those grouped. A decrease in 5-HIAA concentrations was presented in pretreated animals, irrespective of their housing conditions. In conclusion, cocaine administration during pregnancy induces long lasting effects on the offspring, for both behavioral abnormalities and cocaine response, which last to adult life. [Copyright &y& Elsevier]
- Published
- 2005
- Full Text
- View/download PDF
13. Social behavioural profile of cocaine in isolated and grouped male mice
- Author
-
Estelles, J., Rodríguez-Arias, M., Aguilar, M.A., and Miñarro, J.
- Subjects
- *
COCAINE abuse , *AGGRESSION (Psychology) , *ANIMAL models in research , *DRUG abuse - Abstract
Studies concerning the relationship between cocaine and aggression in humans as well as in animals have discrepant outcomes. Increases, decreases, or no changes, have been reported after single or chronic cocaine administration in animal models. To clarify, at least in part, the complex behavioural actions of cocaine, the present study evaluated cocaine effects on social behaviours of mice exposed to different situations (isolated or group housed) using confrontations between two male mice in a neutral area. Different doses of cocaine (6, 25 and 50 mg/kg) were administered in a single or binge pattern (three doses in 24 h) and the behavioural test was performed 20 min after the last injection. No increases in aggression were observed in any situation tested. Instead, cocaine at the two higher doses employed (either in single or binge administration), decreased aggressive behaviours in isolated mice, with no changes being observed in grouped animals. In both types of animals, cocaine increased defensive elements (avoidance/flee) and abolishes social contacts. In conclusion, cocaine presents an anti-aggressive action and may be interpreted as having an anxiogenic-like effect. [Copyright &y& Elsevier]
- Published
- 2004
- Full Text
- View/download PDF
14. Corrigendum to “Effects of Cannabinoid Exposure during Adolescence on the Conditioned Rewarding Effects of WIN 55212-2 and Cocaine in Mice: Influence of the Novelty-Seeking Trait”.
- Author
-
Rodríguez-Arias, M., Roger-Sánchez, C., Villanova, I., Revert, N., Manzanedo, C., Miñarro, J., and Aguilar, M. A.
- Subjects
- *
CANNABINOIDS , *COCAINE - Published
- 2016
- Full Text
- View/download PDF
15. Cocaine enhances the conditioned rewarding effects of MDMA in adolescent mice.
- Author
-
Aguilar, M.A., Roger-Sánchez, C., Rodríguez-Arias, M., and Miñarro, J.
- Subjects
- *
COCAINE abuse , *ECSTASY (Drug) , *CONDITIONED response , *HIPPOCAMPUS (Brain) , *LABORATORY mice - Abstract
Although the consumption of cocaine is frequent in young users of MDMA (3,4-methylenedioxymethamphetamine), the influence of exposure to cocaine on the rewarding effects of MDMA in adolescents has not been studied. The purpose of the present work was to evaluate the effect of co-administration of cocaine (1 and 10 mg/kg) and a sub-threshold dose of MDMA (1.25 mg/kg) on the acquisition of conditioned place preference (CPP) (experiment 1). In addition, the effect of pre-treatment with cocaine on MDMA-induced CPP was evaluated (experiment 2). Levels of monoamines in striatum, hippocampus and cortex were measured in both experiments. Our hypotheses were that cocaine co-administration or pre-treatment would increase the rewarding effects of MDMA, and that these effects would be related with changes in brain monoamine levels. Our results showed that cocaine potentiated the rewarding effects of MDMA, since a sub-threshold dose of MDMA, which did not induce CPP by itself, induced a significant CPP in adolescent mice when administered along with cocaine during conditioning (experiment 1). Moreover, pre-treatment with cocaine several days before conditioning also increased the rewarding effects of MDMA (experiment 2). No significant changes in the levels of biogenic amines, which correlated with these behavioural effects, were observed. Our results confirm the involvement of the dopaminergic system in MDMA-induced CPP in adolescent mice and suggest that combined consumption with or pre-exposure to cocaine increases the conditioned rewarding effects of MDMA, which may enhance the capacity of MDMA to induce dependence. [ABSTRACT FROM AUTHOR]
- Published
- 2015
- Full Text
- View/download PDF
16. P.032 Cannabidiol-mediated effects on behavioural and gene expression changes induced by a new animal model of spontaneous cocaine withdrawal.
- Author
-
Gasparyan, A., Navarrete, F., Rodríguez-Arias, M., Miñarro, J., and Manzanares, J.
- Subjects
- *
COCAINE-induced disorders , *COCAINE , *GENE expression , *ANIMAL models in research - Abstract
B Conclusions: b The results of the present study reveal that CBD significantly improved motor activity, somatic signs and anxiety-like behaviour impairments modulated dopaminergic and cannabinoid targets gene expression changes in the new model of spontaneous cocaine withdrawal. Therefore, CBD alleviates cocaine withdrawal-induced behavioural and gene expression alterations suggesting potential for the management of cocaine withdrawal. [Extracted from the article]
- Published
- 2020
- Full Text
- View/download PDF
17. Role of dopamine neurotransmission in the long-term effects of repeated social defeat on the conditioned rewarding effects of cocaine.
- Author
-
Montagud-Romero, S., Reguilon, M.D., Roger-Sanchez, C., Pascual, M., Aguilar, M.A., Guerri, C., Miñarro, J., and Rodríguez-Arias, M.
- Subjects
- *
COCAINE & psychology , *NEURAL transmission , *DOPAMINERGIC mechanisms , *DRUG administration , *HIPPOCAMPUS (Brain) , *PSYCHOLOGICAL stress - Abstract
Numerous studies report that social defeat stress alters dopamine (DA) neurotransmission in several areas of the brain. Alterations of the mesolimbic dopaminergic pathway are believed to be responsible for the increased vulnerability to drug use observed as a result of social stress. In the present study, we evaluated the influence of DA receptors on the long-term effect of repeated social defeat (RSD) on the conditioned rewarding and reinstating effects of cocaine. For this purpose, the D1R antagonist SCH 23390 and the D1R antagonist raclopride were administered 30 min before each social defeat and a cocaine-induced CPP procedure was initiated three weeks later. The expression of the D1R and D2R was also measured in the cortex and hippocampus throughout the entire procedure. Mice exposed to RSD showed an increase in the conditioned rewarding effects of cocaine that was blocked by both DA receptors antagonists when a subthreshold dose of cocaine was employed. However, while the vulnerability to reinstatement of the preference induced by 25 mg/kg cocaine-induced CPP was abolished by the D1R antagonist, it was practically unaffected by raclopride. Increases in D2R receptor levels were observed in the cortex of defeated animals after the first and fourth social defeats and in the hippocampus 3 weeks later. Nevertheless, D1R receptor levels in the hippocampus decreased only after the last social defeat. Our results confirm that RSD enhances the conditioned rewarding effects of cocaine and that both DA receptors are involved in this enduring effect of social stress. [ABSTRACT FROM AUTHOR]
- Published
- 2016
- Full Text
- View/download PDF
18. `Up-regulation of histone acetylation induced by social defeat mediates the conditioned rewarding effects of cocaine.
- Author
-
Montagud-Romero, S., Montesinos, J., Pascual, M., Aguilar, M.A., Roger-Sanchez, C., Guerri, C., Miñarro, J., and Rodríguez-Arias, M.
- Subjects
- *
DEFEAT (Psychology) , *COCAINE , *CURCUMIN , *DRUG efficacy , *HISTONE acetylation , *BRAIN stimulation , *DRUG administration , *THERAPEUTICS - Abstract
Social defeat (SD) induces a long-lasting increase in the rewarding effects of psychostimulants measured using the self-administration and conditioned place procedures (CPP). However, little is known about the epigenetic changes induced by social stress and about their role in the increased response to the rewarding effects of psychostimulants. Considering that histone acetylation regulates transcriptional activity and contributes to drug-induced behavioral changes, we addressed the hypothesis that SD induces transcriptional changes by histone modifications associated with the acquisition of place conditioning. After a fourth defeat, H3(K9) acetylation was decreased in the hippocampus, while there was an increase of HAT and a decrease of HDAC levels in the cortex. Three weeks after the last defeat, mice displayed an increase in histone H4( K 12) acetylation and an upregulation of histone acetyl transferase (HAT) activity in the hippocampus. In addition, H3(K4)me3, which is closely associated with transcriptional initiation, was also augmented in the hippocampus three weeks after the last defeat. Inhibition of HAT by curcumin (100 mg/kg) before each SD blocked the increase in the conditioned reinforcing effects of 1 mg/kg of cocaine, while inhibition of HDAC by valproic acid (500 mg/kg) before social stress potentiated cocaine-induced CPP. Preference was reinstated when animals received a priming dose of 0.5 mg/kg of cocaine, an effect that was absent in untreated defeated mice. These results suggest that the experience of SD induces chromatin remodeling, alters histone acetylation and methylation, and modifies the effects of cocaine on place conditioning. They also point to epigenetic mechanisms as potential avenues leading to new treatments for the long-term effects of social stress on drug addiction. [ABSTRACT FROM AUTHOR]
- Published
- 2016
- Full Text
- View/download PDF
19. Acute social defeat stress increases the conditioned rewarding effects of cocaine in adult but not in adolescent mice.
- Author
-
Montagud-Romero, S., Aguilar, M.A., Maldonado, C., Manzanedo, C., Miñarro, J., and Rodríguez-Arias, M.
- Subjects
- *
COCAINE , *DRUG dosage , *PSYCHOLOGICAL stress , *LABORATORY mice , *CORTICOSTERONE - Abstract
Stressful experiences modify activity in areas of the brain involved in the rewarding effects of psychostimulants. In the present study we evaluated the influence of acute social defeat (ASD) on the conditioned rewarding effects of cocaine in adolescent (PND 29–32) and adult (PND 50–53) male mice in the conditioned place preference (CPP) paradigm. Experimental mice were exposed to social defeat in an agonistic encounter before each session of conditioning with 1 mg/kg or 25 mg/kg of cocaine. The effects of social defeat on corticosterone levels were also evaluated. Adult mice exposed to ASD showed an increase in the conditioned reinforcing effects of cocaine. Only these mice developed cocaine-induced CPP with the subthreshold dose of cocaine, and they needed a higher number of extinction sessions for the 25 mg/kg cocaine-induced CPP to be extinguished. In adolescent mice, on the other hand, ASD reduced the conditioned reinforcing effects of cocaine, since CPP was not produced with the lower dose of cocaine and was extinguished faster when they were conditioned with 25 mg/kg. Adult mice exposed to social defeat displayed higher levels of corticosterone than their controls and adolescent mice. Our results confirm that the effect of social defeat stress on the acquisition and reinstatement of the CPP induced by cocaine varies depending on the age at which this stress is experienced. [ABSTRACT FROM AUTHOR]
- Published
- 2015
- Full Text
- View/download PDF
20. Critical role of TLR4 in uncovering the increased rewarding effects of cocaine and ethanol induced by social defeat in male mice.
- Author
-
Montagud-Romero, S., Reguilón, M.D., Pascual, M., Blanco-Gandía, M.C., Guerri, C., Miñarro, J., and Rodríguez-Arias, M.
- Subjects
- *
REWARD (Psychology) , *COCAINE , *NEUROGLIA , *TOLL-like receptors , *ETHANOL , *MICE , *SUBSTANCE-induced disorders - Abstract
Substance use disorders and social stress are currently associated with changes in the immune system response by which they induce a proinflammatory state in neurons and glial cells that eventually modulates the reward system. The aim of the present work was to assess the role of the immune TLR4 (Toll-like receptors 4) and its signaling response in the increased contextual reinforcing effects of cocaine and reinforcing effects of ethanol (EtOH) induced by social defeat (SD) stress. Adult male C57BL/6 J wild-type (WT) mice and mice deficient in TLR4 (TLR4-KO) were assigned to experimental groups according to stress condition (exploration or SD). Three weeks after the last SD, conditioned place preference (CPP) was induced by a subthreshold cocaine dose (1 mg/kg), while another set underwent EtOH 6% operant self-administration (SA). Several inflammatory molecules were analyzed in the hippocampus and the striatum. SD induced higher vulnerability to the conditioned rewarding effects of cocaine only in defeated WT mice. Similarly, defeated WT mice exhibited higher 6% EtOH consumption, an effect that was not observed in the defeated TLR4-KO group. However, the motivation to obtain the drug was observed in both genotypes of defeated animals. Notably, a significant upregulation of the protein proinflammatory markers NFkBp-p65, IL-1β, IL-17 A and COX-2 were observed only in the defeated WT mice, but not in their defeated TLR4-KO counterparts. These results suggest that TLR4 receptors mediate the neuroinflammatory response underlying the increase in the rewarding effects of cocaine and EtOH induced by social stress. • Social defeat stress induced higher sensitivity to the reinforcing drug (cocaine and ethanol) effects. • TLR4 receptors are involved in the rewarding effects of cocaine and ethanol induced by social defeat stress. • TLR4 receptors mediate the neuroinflammatory response induced by social stress. [ABSTRACT FROM AUTHOR]
- Published
- 2021
- Full Text
- View/download PDF
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.