Effects of cocaine and morphine in rats from two psychogenetically selected lines: a behavioral and brain dialysis study.

Abstract

The Swiss sublines of Roman high-avoidance (RHA/Verh) and Roman low-avoidance (RLA/Verh) rats differ in their reactivity to environmental and pharmacological stressors, in their sensitivity to stereotypies elicited by dopamine (DA)-mimetic agents, and in their densities of D1 DA receptors in the terminal field of the mesoaccumbens DAergic projection, an important link in the neural networks involved in the motor effects and reinforcing properties of drugs abused by humans. The present study was therefore designed to compare the behavioral and neurochemical 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 microdialysis. The number of counts corresponding to horizontal, vertical, and total motor activities accumulated in basal conditions during the 60-min acclimation period was significantly larger in RHA/Verh than in RLA/Verh rats. Moreover, horizontal, vertical, and total motor activities throughout the 120-min observation period that followed the administration 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 significantly more intense after acute cocaine and morphine challenges than 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 the basal DA output, but the effect of cocaine on DA release was more robust in RHA/Verh rats. Likewise, the effect of morphine was more pronounced in RHA/Verh than in RLA/Verh rats. Because the mesoaccumbens DAergic pathway plays a central role in the acquisition of motivational valence 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 information on the biological correlates of drug dependence.