Chronic pubertal, but not adult chronic cannabinoid treatment impairs sensorimotor gating, recognition memory, and the performance in a progressive ratio task in adult rats.
There is evidence from studies in humans and animals that a vulnerable period for chronic cannabinoid administration exists during certain phases of development. The present study tested the hypothesis that long-lasting interference of cannabinoids with the developing endogenous cannabinoid system during puberty causes persistent behavioral alterations in adult rats. Chronic treatment with the synthetic cannabinoid agonist WIN 55,212-2 (WIN) (1.2 mg/kg) or vehicle was extended over 25 days either throughout the rats' puberty or for a similar time period in adult rats. The rats received 20 injections intraperitoneally (i.p.), which were not delivered regularly. Adult rats were tested for object recognition memory, performance in a progressive ratio (PR) operant behavior task, locomotor activity, and prepulse inhibition (PPI) of the acoustic startle response (ASR). PPI was significantly disrupted only by chronic peripubertal cannabinoid treatment. This long-lasting PPI deficit was reversed by the acute administration of the dopamine antagonist haloperidol. Furthermore, we found deficits in recognition memory of pubertal-treated rats and these animals showed lower break points in a PR schedule, whereas food preference and locomotion were not affected. Adult chronic cannabinoid treatment had no effect on the behaviors tested. Therefore, we conclude that puberty in rats is a vulnerable period with respect to the adverse effects of cannabinoid treatment. Since PPI deficits, object recognition memory impairments, and anhedonia/avolition are among the endophenotypes of schizophrenia, we propose chronic cannabinoid administration during pubertal development as an animal model for some aspects of the etiology of schizophrenia.
Schneider
Miriam
M
Brain Research Institute, Department of Neuropharmacology, University of Bremen, Bremen, Germany. miriam.schneider@uni-bremen.de
Koch
Michael
M
D000161:Acoustic Stimulation; D000818:Animals; D000831:Animals, Newborn; D048588:Benzoxazines; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002186:Cannabinoids / Q000494:pharmacology*; D003216:Conditioning, Operant / Q000187:drug effects; D005260:Female; D008297:Male; D008568:Memory / Q000187:drug effects / Q000502:physiology*; D009025:Morpholines / Q000494:pharmacology; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D009281:Naphthalenes / Q000494:pharmacology; D011597:Psychomotor Performance / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D012022:Reflex, Acoustic / Q000187:drug effects / Q000502:physiology*; D013995:Time; D013997:Time Factors
D048588:Benzoxazines; D002121:Calcium Channel Blockers; D002186:Cannabinoids; D009025:Morpholines; D009281:Naphthalenes; C070417:(3R)-((2,3-dihydro-5-methyl-3-((4-morpholinyl)methyl)pyrrolo-(1,2,3-de)-1,4-benzoxazin-6-yl)(1-naphthalenyl))methanone