Chronic pubertal, but not adult chronic cannabinoid treatment impairs sensorimotor gating, recognition memory, and the performance in a progressive ratio task in adult rats
Source: NEUROPSYCHOPHARMACOLOGY Volume: 28 Issue: 10 Pages: 1760-1769 Published: OCT 2003
Abstract: 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.
Document Type: Article
Language: English
Author Keywords: WIN 55,212-2; recognition memory; prepulse inhibition; reward; schizophrenia; puberty
KeyWords Plus: SPATIAL WORKING-MEMORY; OBJECT-RECOGNITION; PREFRONTAL CORTEX; PREPULSE INHIBITION; DOPAMINE NEURONS; CHRONIC DELTA(9)-TETRAHYDROCANNABINOL; SCHIZOPHRENIC-PATIENTS; RECEPTOR ANTAGONIST; ACOUSTIC STARTLE; BRAIN
Reprint Address: Schneider, M (reprint author), Univ Bremen, Dept Neuropharmacol, Brain Res Inst, POB 33 04 40, D-28334 Bremen, Germany
Addresses:
1. Univ Bremen, Dept Neuropharmacol, Brain Res Inst, D-28334 Bremen, Germany
Publisher: NATURE PUBLISHING GROUP, MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
Subject Category: Neurosciences; Pharmacology & Pharmacy; Psychiatry
IDS Number: 729XG
ISSN: 0893-133X
DOI: 10.1038/sj.npp.1300225
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