1. ¹School of Psychology, University of Sydney, Sydney, NSW, Australia
2. ²Department of Pathology, University of Sydney, Sydney, NSW, Australia
3. ³Department of Pharmacology, University of Sydney, Sydney, NSW, Australia
4. ⁴Drugs and Driving Toxicology Laboratory, NSW Government Division of Analytical Laboratories, Sydney, NSW, Australia
5. ⁵Department of Psychology, Wilfrid Laurier University, Waterloo, ON, Canada

Correspondence: Professor IS McGregor, School of Psychology, University of Sydney, A18, Sydney, NSW 2006, Australia. Tel: +61 2 9351 3571; Fax: +61 2 9351 8023; E-mail: iain@psych.usyd.edu.au

Received 11 January 2007; Revised 9 April 2007; Accepted 14 May 2007; Published online 20 June 2007.

Abstract

The current study examined whether adolescent rats are more vulnerable than adult rats to the lasting adverse effects of cannabinoid exposure on brain and behavior. Male Wistar rats were repeatedly exposed to -9-tetrahydrocannabinol (⁹-THC, 5 mg/kg i.p.) in a place-conditioning paradigm during either the adolescent (post-natal day 28+) or adult (post-natal day 60+) developmental stages. Adult rats avoided a ⁹-THC-paired environment after either four or eight pairings and this avoidance persisted for at least 16 days following the final ⁹-THC injection. In contrast, adolescent rats showed no significant place aversion. Adult ⁹-THC-treated rats produced more vocalizations than adolescent rats when handled during the intoxicated state, also suggesting greater drug-induced aversion. After a 10–15 day washout, both adult and adolescent ⁹-THC pretreated rats showed decreased social interaction, while only ⁹-THC pretreated adolescent rats showed significantly impaired object recognition memory. Seventeen days following their last ⁹-THC injection, rats were euthanased and hippocampal tissue processed using two-dimensional gel electrophoresis proteomics. There was no evidence of residual ⁹-THC being present in blood at this time. Proteomic analysis uncovered 27 proteins, many involved in regulating oxidative stress/mitochondrial functioning and cytoarchitecture, which were differentially expressed in adolescent ⁹-THC pretreated rats relative to adolescent controls. In adults, only 10 hippocampal proteins were differentially expressed in ⁹-THC compared to vehicle-pretreated controls. Overall these findings suggest that adolescent rats find repeated ⁹-THC exposure less aversive than adults, but that cannabinoid exposure causes greater lasting memory deficits and hippocampal alterations in adolescent than adult rats.