Different influence of adolescent exposure to heroin and Delta9-THC on heroin self-administration behavior in adulthood

SCIFO, ANDREA;LECCA, DANIELE;Cadoni C;VALENTINI, VALENTINA;Piras G;Pisanu A;Di Chiara G.

2014-01-01

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Abstract

AIM: Lewis (LEW) and Fischer (F344) inbred rats show several neurochemical and behavioral differences concerning the reinforcing properties of drug of abuse. Using these genetic model strains we evaluated the influence of adolescent pre-exposure to heroin and Delta9-THC on adulthood heroin self-administration (SA) behavior. METHODS: On the 6th postnatal (PN) week rats were administered twice daily with increasing doses of heroin (Exp-I: 5,10,20 mg/kg, s.c.) and Δ9-THC (Exp-II: 2,4,8 mg/kg, i.p.) for three consecutive days. In adulthood (10th PN week), LEW and F344 rats were trained to acquire heroin SA under Fixed Ratio (FR) schedule of responding. In Exp-I, after FR sessions rats were submitted to extinction and reinstatement phases, while in Exp-II rats were also allowed to self-administer heroin under Progressive Ratio (PR) schedule, then underwent to extinction and reinstatement. RESULT: In both experiments, LEW rats showed higher responding and faster acquisition of heroin self-administration as compared to F344 rats, but no differences between F344 pre-treated and F344 control were found. In Exp-I, LEW pretreated rats strongly increased SA compared to their controls as well as to F344 groups. Furthermore, in Exp-II, LEW Δ9-THC pretreated rats readily acquire PR schedule, showed greater nose poking behavior and higher breaking point values compared to controls and both F344 experimental groups. CONCLUSION: These results strongly suggest that heroin and Δ9-THC pre-treatment in adolescence differentially affects heroin reinforcement in adulthood in a strain-related way, emphasizing the importance of genetic factors in the development of drug addiction.