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ABSTRACT Several lines of evidence suggest that there may be a shared vulnerability to acquire behaviors motivated by strong incentive stimuli. Non-food restricted male Sprague-Dawley rats ( n = 78) underwent place conditioning with Oreos, and were subsequently tested on cocaine self-administration (SA) on fixed and progressive ratios, as well as extinction and reinstatement by cocaine primes and by consumption of Oreos. Although there was a group preference for the Oreo-paired compartment, at the individual level some rats (69%) displayed a preference and others did not. In cocaine SA, 'preference' rats achieved higher break points on a progressive ratio, and displayed greater responding during extinction and cocaine-induced reinstatement. Within the context of this study, Oreo-cocaine cross-reinstatement was not observed. In a control study, rats ( n = 29) conditioned with a less palatable food (rice cakes) also displayed individual differences in place preference, but not on subsequent cocaine tests. These findings indicate that there is a relationship between incentive learning promoted by palatable foods and by cocaine. This supports the hypothesis that co-morbid food-drug addictions may result from a shared vulnerability to acquire behaviors motivated by strong incentives. [ABSTRACT FROM AUTHOR]

It has been proposed that the reinforcing properties of drugs of abuse are due, in part, to their ability to enhance memory consolidation. To test this hypothesis, heroin (0.03–3 mg/kg, SC) and d-amphetamine (0.5–2 mg/kg, SC) were administered to male Sprague-Dawley rats immediately or 4 h after training on win-stay and fear conditioning tasks. On the win-stay, immediate post-training administration of lower doses of heroin and d-amphetamine enhanced acquisition, and probe tests further revealed that these drugs enhanced different aspects of learning. Higher doses had no effect or impaired performance, particularly when administered repeatedly. On fear conditioning, the memory-enhancing effects of immediate post-training administration of lower heroin and d-amphetamine doses were revealed only when a single tone–shock pairing procedure was employed. Therefore, under appropriate experimental conditions, mildly stimulatory doses of heroin and d-amphetamine enhanced the acquisition of tasks thought to involve different types of learning. These results support the hypothesis that one of the ways in which drugs of abuse such as opiates and psychomotor stimulants reinforce behavior is by enhancing memory consolidation processes. [ABSTRACT FROM AUTHOR]

Abstract: Perseveration refers to maladaptive persistence of behavior outside appropriate contexts and despite negative outcomes. In humans, perseveration is a symptom of a variety of psychiatric disorders. In rats, perseveration has been observed in reversal learning tasks following lesions of the prefrontal cortex (PFC). However, the exact nature of the impairment underlying this effect remains unclear. Male Sprague–Dawley rats were trained on a novel reversal task that requires switching between two rewarded options varying in effort (concurrent fixed and progressive ratios) necessary to obtain the reward. Following initial training, bilateral lesions of the dorsal PFC, medial PFC, or orbitofrontal cortex were produced by NMDA infusions. When animals were re-tested post-surgery, no significant impairments were found. These results indicate that, in trained rats, the PFC is not necessary for selecting responses on the basis of favorable effort-to-reward contingencies. [Copyright &y& Elsevier]

Abstract: Cocaine exposure impairs the ability to match responding when rewarded and non-rewarded response options are reversed. However, it is unclear whether the impairment can also be observed when two rewarded responses differing in delay or magnitude of reward are reversed. Therefore, we tested the effect of acute (Experiment 1) and repeated (Experiment 2) cocaine on response matching between options dynamically varying in reinforcement schedule. Male Sprague–Dawley rats responded on concurrent fixed ratio 25 (FR25) and variable ratio 15 (VR15) schedules for sucrose. On tests, a progressive ratio (PR) schedule replaced the VR15, creating a within-session dynamic reversal point. In Experiment 1, acute cocaine (0, 1, 3 or 15mg/kg IP) did not alter response matching. In Experiment 2, rats chronically exposed to cocaine (30mg/kg/day×5days, IP) were tested after a 10-day withdrawal period on three sets of FR25/PR matching tasks with varying rates of PR escalation. Cocaine pre-exposure significantly increased perseverative matching errors, although repeated testing compensated the impairment. These results suggest that prior exposure to cocaine can produce perseverative behavior even when animals are required to match two well-learned and rewarded response options. The implications for addictive behaviors are discussed. [Copyright &y& Elsevier]

Abstract: The aim of the present experiment was to investigate the effects of cocaine primes and exposure to foot shock stress on reinstatement of operant responding maintained by a cocaine-conditioned stimulus in rats never trained to actively self-administer cocaine. Following a baseline session of responding for a light-buzzer compound stimulus, rats underwent classical conditioning whereby the compound stimulus was paired with passive intravenous infusions of cocaine (vehicle, 0.5 or 1.0 mg/kg/inf). On subsequent test sessions, operant responding for the compound stimulus was re-assessed in the absence of cocaine. Finally, rats received a cocaine prime (20 mg/kg, i.p.) and foot shock stress prior to two separate test sessions assessing lever pressing for the cocaine-conditioned stimulus. It was found that the animals conditioned with cocaine displayed sustained responding on the lever activating the cocaine-conditioned stimulus. In addition, priming injections of cocaine reinstated responding for the light-buzzer compound stimulus, and this effect was proportional to the dose of cocaine received during classical conditioning. Foot shock stress also reinstated responding, but its effect was smaller and observed only in animals conditioned with the highest dose of cocaine. These findings suggest that cocaine primes and stress can induce reinstatement by reactivating the motivational value of cocaine-conditioned cues. [Copyright &y& Elsevier]

Abstract: To investigate the process of relapse to drug seeking caused by reexposure to drugs, we studied the consequences of recurring instances of stimuli–drug associations using heroin conditioned place preference (CPP) in rats. After original conditioning and extinction, rats received either a single compartment–heroin pairing (reconditioning) or were primed with heroin and tested for reinstatement of CPP. It was found that the session of reconditioning, but not the session of reinstatement, caused the reappearance of a preference for the heroin-paired compartment on a test given 24 h later, in drug-free conditions. The effect of reconditioning was found to be dependent on heroin doses, and was not seen when heroin injections were given outside the conditioning environment. Furthermore, a single session of reconditioning elevated heroin seeking even on a test given 96 h later. Finally, heroin seeking was found to be significantly elevated on a test given 28 days after the last extinction session whether animals received 1 or 3 reconditioning sessions. These results suggest that the motivational value of cues associated with heroin is not eliminated by extinction and, importantly, that these cues can rapidly regain their ability to promote drug seeking behavior if they are re-associated with the effect of heroin. [Copyright &y& Elsevier]

We investigated whether chronic exposure to heroin alters responses to cocaine in ways that might explain the use of cocaine by opioid addicts. To this end, the effects of cocaine (5 and 20 mg/kg) were assessed on locomotor activity of rats chronically exposed to heroin (0.0, 3.5, 7.0, and 14.0 mg/kg/day, over 14 days, via osmotic mini-pumps), or withdrawn from heroin (1 day, acute withdrawal, and 14 days, protracted withdrawal). Chronic heroin exposure, in itself, dose dependently increased locomotion and acute cocaine administration further elevated locomotor activity in a dose-dependent and additive manner. During acute withdrawal, there was a dose-dependent decrease in locomotion that was reversed by cocaine in a dose-dependent manner. During protracted withdrawal, spontaneous locomotion normalized, but rats previously exposed to heroin displayed cross-sensitization to cocaine as indicated by small, but significant, enhanced locomotor response to 5 mg/kg of cocaine, and enhanced intravenous self-administration of low doses of cocaine (0.13 mg/kg/infusion). In a separate study, we measured extracellular dopamine (DA) in the nucleus accumbens (Acb) using in vivo microdialysis before and after acute withdrawal from heroin. During chronic exposure to heroin, basal extracellular DA was elevated dose dependently, whereas in acute withdrawal, levels were not different from those in vehicle-treated rats. In response to cocaine, however, DA activity in the Acb was significantly lower in rats withdrawn from the highest dose of heroin. [ABSTRACT FROM AUTHOR]

There is mounting evidence that diets supplemented with polyunsaturated fatty acids (PUFA) can impact brain biology and functions. This study investigated whether moderately high-fat diets differing in n-6/n-3 fatty acid ratio could impact fatty acid composition in regions of the brain linked to various psychopathologies. Adult male Sprague Dawley rats consumed isocaloric diets (35% kcal from fat) containing different ratios of linoleic acid (n-6) and alpha-linolenic acid (n-3) for 2 months. It was found that the profiles of PUFA in the prefrontal cortex, hippocampus, and hypothalamus reflected the fatty acid composition of the diet. In addition, region-specific changes in saturated fatty acids and monounsaturated fatty acids were detected in the hypothalamus, but not in the hippocampus or prefrontal cortex. This study in adult rats demonstrates that fatty acid remodeling in the brain by diet can occur within months and provides additional evidence for the suggestion that diet could impact mental health. [ABSTRACT FROM AUTHOR]

Abstract: To investigate the role of the basolateral amygdala (BLA) in the reacquisition of heroin seeking, we studied the effect of BLA inactivation after heroin re-exposure in the presence of drug-conditioned cues. We employed a heroin conditioned place preference task [Leri F, Rizos Z, 2005. Reconditioning of drug-related cues: a potential contributor to relapse after drug re-exposure. Pharmacol Biochem Behav 2005;80:621–30.], where after initial conditioning and subsequent extinction, rats received a single reconditioning session (explicit compartment–heroin re-pairing), followed by a test of heroin seeking 24 h later. Rats were infused with GABAA/GABAB agonists (muscimol and baclofen, 0.03 and 0.3 nmol, respectively/0.3 μl) or vehicle, either 15 min or 6 h following the heroin reconditioning session. Animals that received vehicle infusions, whether they were given 15 min or 6 h following reconditioning, showed a significant preference for the heroin-paired compartment 24 h later. However, inactivation of the BLA 15 min post-reconditioning, but not 6 h following reconditioning, completely blocked the reacquisition of heroin seeking. These results suggest that the BLA plays an important role in a putative learning process initiated by drug re-exposure which may underlie the process of relapse. [Copyright &y& Elsevier]

Abstract: To investigate the effect of naloxone on a putative memory consolidation process underlying reacquisition of heroin and cocaine conditioned place preference, four studies were conducted in male Sprague–Dawley rats using a common procedure involving: place conditioning (0.3 or 1mg/kg heroin or 20mg/kg cocaine; ×4 sessions), extinction (vehicle×4 sessions), and reconditioning (0 or 1mg/kg heroin or 20mg/kg cocaine; ×1 session). Systemic naloxone injections (0, 1 and 3mg/kg) or bilateral intra-ventral tegmental area (VTA) naloxone methiodide infusions (2nmol in 0.5μl×side) were administered at different times following reconditioning. Post-reconditioning administration of naloxone dose-dependently blocked, attenuated and had no effect on reacquisition of heroin CPP when administered immediately, 1h and 6h after reconditioning, respectively. The highest dose of naloxone also blocked reacquisition of cocaine CPP, and did not produce a conditioned place aversion in heroin-naïve and heroin pre-treated animals. Post-reconditioning infusions in the VTA, but not in adjacent structures, blocked reacquisition of heroin CPP when administered immediately, but not 6h, after reconditioning. These data suggest that reacquisition of drug-cues associations involves a memory consolidation process sensitive to manipulations of the endogenous opioid system, and indicate that opioid receptors in the VTA may be critically involved in the re-emergence of drug seeking behavior. [Copyright &y& Elsevier]

Abstract: Converging evidence suggests that the endogenous cannabinoid (eCB) system is involved in extinction of learned behaviours. Using operant and classical conditioning procedures, the potential of the fatty acid amide (FAAH) inhibitor, URB-597, and the CB1 antagonist/inverse agonist, SR141716, to promote and inhibit (respectively) extinction of learned responses previously motivated by either rewarding or aversive stimuli was investigated. In the operant conditioning procedure (Expt. 1), rats previously trained to lever press for sucrose reward were administered URB-597 (0.3 mg/kg) or the CB1 antagonist/inverse agonist SR141716 (2.5 mg/kg) prior to each of three extinction trials. In the conditioned floor preference procedure (Expts 2a–d), rats trained to associate morphine with one of two distinctive floors were administered one of several doses of the CB1 antagonist/inverse agonist, AM-251 (Expt 2a) or URB-597 (Expt 2b and 2d) prior to each extinction/test trial wherein a choice of both floors was presented and prior to forced exposure to each floor (Expt 2c). In the conditioned floor aversion procedure (Expt. 3), rats trained to associate a naloxone-precipitated morphine withdrawal with a floor cue were administered URB-597 or SR141716 prior to each of 24 extinction/testing trials. URB-597 did not promote and SR141716 did not reduce extinction rates for sucrose reward-induced operant responding (Expt. 1) or morphine-induced conditioned floor preference (Expts. 2a–d). In contrast, URB-597 facilitated, whereas SR141716 impaired, extinction of the conditioned floor aversion (Expt. 3). These data support previous reports that the eCB system selectively facilitates extinction of aversive memories. URB-597 may prove useful in targeting extinction of aversively motivated behaviours. [Copyright &y& Elsevier]