Search

The Roman high- and low-avoidance (RHA/Verh and RLA/Verh) rat lines represent, respectively, low emotional/anxious and high novelty seeker vs. high emotional/anxious and low novelty seeker profiles. In the present study, RLA/Verh and RHA/Verh rats, either reared in pairs from weaning (untreated) or reared in groups of 8-10 in an enriched environment until the age of 7 months, were tested for exploratory and novelty-seeking behavior in the hole board (including novel objects under the holes), as well as for their preference for saccharin-water and ethanol-water in a two-bottle free-choice paradigm. Testing started when rats were 20 months old in order to study the long-lasting effects of differential rearing. RHA/Verh rats explored more and showed greater preference for (and intake of) saccharin as well as for ethanol than RLA/Verh rats, thus confirming their validity as a rat model for sensation/reward seeking. Environmental enrichment (EE) increased head-dipping behavior (i.e., novelty seeking) in both rat lines, without affecting locomotor activity. EE treatment increased the preference for, and volume intake of, saccharin (especially at the higher concentrations tested) in the relatively low saccharin-preferring RLA/Verh rats, and also enhanced ethanol consumption in both rat lines. Thus, the results demonstrate consistent and enduring effects of EE on incentive-seeking behavior and further the analysis of how individual differential predispositions for the need of novelty and contact with (or consumption of) rewarding substances arise through either biological (genetic) or early environmental factors, or both.

The present study investigated the effects of perinatal flumazenil (Ro 15-1788, a benzodiazepine receptor antagonist), given from gestational day 15 to the 14th day after giving birth, at two doses (3.5 and 6.3 mg/kg/ day) on the behavior of female RLA/Verh rats. This rat line has been selectively bred for non-acquisition of two-way active avoidance. Offspring of treated/non-treated dams were tested when adults for two-way active (shuttle box) avoidance acquisition. For comparison reasons additional offspring coming from the same treatments were used in an hyponeophagia test and in both an open field and a plus maze tests. The results show that perinatal flumazenil, specially the lower dose (and also the highest dose, although only in the final phases of the shuttle box training) was able to improve two-way active avoidance acquisition, as it has been previously found with males, whereas it failed to show any effect in the hyponeophagia task, the open field and the plus-maze tests. As two-way active avoidance acquisition can be enhanced both by reducing emotionality/anxiety or by improving memory, it is suggested that flumazenil treatment could have affected either one or both processes.

The present studies evaluated the short- and long-lasting effects of postnatal handling (administered during the first 21 days of life) on the emotional behavior of female Sprague-Dawley rats. The performance of postnatally handled (H) and control nonhandled (NH) animals was compared in two different situations: an emotionality rating (ER) test (when they were 40 days or 4 months old), and a hyponeophagia (neophobia) test of anxiety, at the age of 4 months. The results showed that postnatal handling induced both short-term and long-term reductions of spontaneous emotional reactivity in the ER test, although the effects on some measures disappeared in 4-month-old rats. Postnatal handling also induced enduring decreases of anxiety as measured by the hyponeophagia test. None of the observed effects were attributable to changes in basal locomotor activity. ER measures were significantly related to hyponeophagia, because animals showing the highest emotionality scores in the ER test (preferentially NH animals) were those that showed the highest eating latencies and spent less time eating in the neophobic situation (i.e., hyponeophagia test).

The effects of low (2 g/kg) and high (4 g/kg) doses of ethanol and their interaction with the imidazobenzodiazepine Ro 15-4513 (a partial inverse agonist of the benzodiazepine receptor) were studied in two different models of anxiety in rats: the "elevated plus-maze" test and the early acquisition of two-way (shuttlebox) avoidance. In the elevated plus-maze, ethanol (2 g/kg) increased the percentage of entries into the open arms (%EOA) and both ethanol doses increased the percentage of time spent into the open arms (%TOA), thus indicating an anxiolytic action which was reversed by Ro 15-4513 (5 mg/kg). By contrast, Ro 15-4513 did not counteract the anxiolytic effect of the low dose of ethanol in the acquisition of shuttlebox avoidance. Thus, the treatment with 2 g/kg of ethanol (plus either vehicle or Ro 15-4513) significantly increased the total number of avoidances. Conversely, animals treated with 4 g/kg of ethanol showed impaired shuttlebox avoidance acquisition, and this effect was completely reversed by Ro 15-4513. Ro 15-4513 was without effect on its own in any of the anxiety-related parameters (i.e., %EOA, %TOA, and avoidance acquisition). The results indicate a different pattern of ethanol effects and Ethanol x Ro 15-4513 interactions depending upon the task used.

Rats pretreated either with the anxiolytic triazolobenzodiazepine alprazolam (0.75 and 1.75 mg kg-1 i.p.) or ethanol (1, 2, 3 and 4 g kg-1 p.o.) were tested in both the elevated plus-maze and the early acquisition of shuttlebox avoidance. Both substances induced overall anxiolytic effects in the plus-maze, with the 0.75 mg kg-1 being the most effective alprazolam dose and 1-3 g kg-1 being the most effective ethanol doses. Both drugs were also anxiolytic in the shuttlebox, since 1.75 mg kg-1 alprazolam and 2-3 g kg-1 ethanol improved acquisition of the task. Correlational and factor analysis showed that behaviour in the open arms of the plus-maze and efficiency in shuttlebox avoidance acquisition are positively associated, thus providing further support to the contention that the early acquisition of shuttlebox avoidance is an animal model of anxiety.

The effects of diazepam (DZ, 4 mg/kg), alprazolam (ALP, 1.25 mg/kg) and adinazolam (ADIN, 6 mg/kg), as well as their interaction with the benzodiazepine receptor antagonist flumazenil (Ro15-1788), were studied on the early acquisition of two-way active (shuttlebox) avoidance in male Sprague-Dawley rats. The three benzodiazepines increased shuttlebox avoidance acquisition, and their effects were prevented (antagonized) by flumazenil (10 mg/kg). The present results indicate that central benzodiazepine (BZ) receptors are involved in the anxiolytic effects of diazepam and triazolobenzodiazepines on the early acquisition of two-way active avoidance.

Problems in the application of exposure techniques to the management of long term dishabituation in addicts are discussed in the light of human and animal evidence. Extinction and habituation of responses to drug cues or drug aftereffects are unstable and strongly dependent on context, thus limiting the effectiveness of cue exposure treatments in the prevention of relapse. Several strategies are suggested to improve the stability of extinction and habituation in order to enduringly prevent relapse in addictions. (i) Warning patients about the episodic resurgence of unexpected urges or cravings precipitated by conditioned contexts and exposing them to such contexts. (ii) To obtain a maximum protection against relapse, extinction should 'recreate' all the original learning contexts (i.e. all possible drug cues). (iii) The behavioral chains involved in self administering drugs ought to be incorporated into cue exposure treatments (without permitting consummatory responses) in order to decrease their signal value as cues for drugs.

The effect of infantile handling stimulation and/or perinatal flumazenil (Ro 15-1788; a benzodiazepine receptor antagonist; 3.7 mg/kg/day) administration on exploratory and emotional-related behavior was investigated using adult females from the Roman high- and low-avoidance (RHA/Verh and RLA/Verh) lines. When rats (6 months old) were exposed to a hexagonal tunnel maze including an illuminated central arena, it was found that RHA/Verh rats were more active, explored more maze area, showed more outward preference, and more frequently entered the illuminated center than RLA/Verh rats. In addition, postnatal stimulation decreased emotional-related behavior in both lines of rats, as expressed by increased entry into, and time spent in, the central arena. Perinatal flumazenil treatment decreased entry into the maze central arena in both rat lines but this effect was counteracted by postnatal (handling) stimulation. Thus, the present study extends to adult RHA/Verh and RLA/Verh rats the positive long-lasting effects of postnatal handling and shows postnatal handling x flumazenil interactions in some behavioral parameters related to the pattern of exploration and exploratory efficiency.

The acquisition of two-way active (shuttlebox) avoidance involves a conflict situation which can be used as an animal model of anxiety, since it is sensitive to manipulations of the animal's emotivity/reactivity. The results from the present study (experiment 1) add relevant support to that proposal, since diazepam (2 and 4 mg/kg) and the triazolobenzodiazepine alprazolam (1, 1.25 and 1.5 mg/kg) significantly improved avoidance performance in shuttlebox acquisition in rats in agreement with previous data. In another study (experiment 2), a mild stressful (10-day) handling procedure (i.e. handling which tends to increase the emotional reactivity of the animals, as showed in experiment 3) was found to affect such behaviour in an opposite direction to that of the two benzodiazepines. Conversely, when an habituating handling procedure (i.e. handling which leads to less reactive animals; experiment 3) was used, the acquisition of shuttlebox avoidance was improved (experiment 4). The results are discussed in relation with previous data showing that the particular parameters used in the exposure to stressful stimuli may lead to either sensitization or habituation of anxious responses.