Cannabinoid-induced conditioned place preference in the spontaneously hypertensive rat–an animal model of attention deficit hyperactivity disorder
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Cannabis preparations are the most widely consumed illicit drugs, and their use typically begins in adolescence. The prevalence of cannabis abuse is higher in patients with attention deficit/hyperactivity disorder (ADHD) than in the general population, yet, knowledge about the motivational properties of cannabinoids in animal models of ADHD are lacking.
To compare the motivational effects of the synthetic cannabinoid agonist WIN55,212-2 (WIN) in adolescent and adult spontaneously hypertensive rats (SHR), a validated animal model of ADHD, and Wistar rats, representing a “normal” genetically heterogeneous population. We also asked whether the effects of WIN depended (1) on the activation of the cerebral subtype of cannabinoid receptors, namely, the CB1 cannabinoid receptor and (2) on putative changes by WIN in blood pressure.
WIN was tested under an unbiased conditioned place preference (CPP) paradigm. Blood pressure after WIN administration was also monitored in additional groups of rats.
In the Wistar rats, WIN produced place aversion only in the adult but not adolescent rats. In contrast, WIN produced CPP in both adolescent and adult SHR rats. The behavioral effects of WIN were CB1-mediated and not related to blood pressure.
The contrasting effects of WIN in Wistar and SHR, and the higher resistance of adolescent rats to the aversive and rewarding effects of WIN in these two strains suggests that both adolescence and the ADHD-like profile exhibited by the SHR strain constitute factors that influence the motivational properties of cannabinoids.
KeywordsAttention deficit hyperactivity disorder (ADHD) Drug addiction Adolescence Cannabinoid system Dopamine Reward Aversion Conditioned place preference Inbred strain Spontaneously hypertensive rat (SHR)
The authors are grateful to Dr. Jamil Assreuy for his expert assistance in blood pressure measurements and to Dr. Attila Köfalvi and Dr. Kelly J. Clemens for helpful comments. P.P. and R.S. are supported by scholarships from CNPq, Brazil. L.F.V. had a post-doctoral fellowship from FONDATION FYSSEN, France. R.N.T. is the holder of a CNPq fellowship.
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