EFFECTS OF COCAINE AND MORPHINE IN RATS FROM 2 PSYCHOGENETICALLY SELECTED LINES - A BEHAVIORAL AND BRAIN DIALYSIS STUDY

The Swiss sublines of Roman high-avoidance (RHA/Verh) and Roman low-av oidance (RLA/Verh) rats differ in their reactivity to environmental an d pharmacological stressors, in their sensitivity to stereotypies elic ited by dopamine (DA)-mimetic agents, and in their densities of D-1 DA receptors in the terminal field of the mesoaccumbens DAergic projecti on, an important link in the neural networks involved in the motor eff ects and reinforcing properties of drugs abused by humans. The present study was therefore designed to compare the behavioral and neurochemi cal effects of cocaine (5 mg/kg, i.p.) and morphine (0.5 mg/kg, s.c.) in RHA/Verh and RLA/Verh rats. To this aim, we measured motor activity and DA output in the nucleus accumbens as determined by brain microdi alysis. The number of counts corresponding to horizontal, vertical, an d total motor activities accumulated in basal conditions during the 60 -min acclimation period was significantly larger in RHA/Verh than in R LA/Verh rats. Moreover, horizontal, vertical, and total motor activiti es throughout the 120-min observation period that followed the adminis tration of vehicle tended to be larger in RHA/Verh rats, although the difference between the two lines was not statistically significant. In RHA/Verh rats, locomotion, rearing, and total motor activity were sig nificantly more intense after acute cocaine and morphine challenges th an after vehicle administration, whereas no significant differences in motor activity were observed between control and cocaine-or morphine- treated RLA/Verh rats. No line-related differences were detected in th e basal DA output, but the effect of cocaine on DA release was more ro bust in RHA/Verh rats. Likewise, the effect of morphine was more prono unced in RHA/Verh than in RLA/Verh rats. Because the mesoaccumbens DAe rgic pathway plays a central role in the acquisition of motivational v alence by environmental and pharmacological stimuli and, therefore, in operant behavior, our results suggest that comparative behavioral and neurochemical studies in these two lines may provide useful informati on on the biological correlates of drug dependence.