Behavioural effects of acute and repeated cocaine treatments: a comparative study in sensitisation-prone RHA rats and their sensitisation-resistant RLA counterparts

Rationale: Dopamine (DA) transmission is critically involved in the motor effects of psychostimulants and opiates, as well as in the augmentation of these effects resulting from repeated drug administration-a process termed behavioural sensitisation. The latter is known to play a central role in the development and maintenance of drug addiction as well as in the high frequency of relapse observed in drug addicts following detoxification. The selective breeding of Roman high-(RHA) and low-avoidance (RLA) rats for extreme performances in the acquisition of avoidant behaviour has generated two phenotypes that differ in the functional properties of the mesocortical and mesolimbic DA systems and in their behavioural and neurochemical responses to the acute administration of psychostimulants and opiates. More recently, we showed that repeated morphine or amphetamine injections induce behavioural sensitisation in RHA, but not RLA, rats. Objective: To further characterize the differences in the susceptibility to develop psychostimulant sensitisation between the Roman lines, we evaluated the behavioural effects of acute cocaine ( 5 and 10 mg kg(-1), i.p.) 1 day before and 8 days after repeated administration of saline (2 ml kg(-1), i.p.) or cocaine (10 mg kg(-1), i.p. for 14 consecutive days). Results: We show that repeated cocaine administration elicits augmented behavioural responses to both challenge doses of the same drug only in RHA rats. Conclusions: The Roman lines represent a useful model to investigate how, and to what extent, the genetic make-up influences the neural substrates of individual vulnerability to addiction