Background: Vulnerability to drug addiction depends on acquired as well as genetic factors (Swendsen & Le Moal 2010). Among acquired factors is previous exposure to other drugs of abuse. Thus, exposure to Cannabis has been suggested to predispose to heroin abuse and dependence (Gateway Hypothesis) (Kandel et al. 2006). Here we studied the influence of adolescent delta 9-THC exposure on heroin reward and renforcement and on the in vivo dopamine stimulant properties of heroin in two inbred rat strains differentially vulnerable to drugs of abuse, the addiction prone Lewis and the addiction resistant Fisher344 strain. Results: THC increased extracellular DA, as estimated by microdialysis, in Lewis but not in Fischer 344 rats. Adolescent THC exposure potentiated DA stimulant effects of heroin in the shell and core of Lewis and only in the core of Fischer344 rats. Control Lewis rats developed stronger conditioned place preference (CPP) to heroin and resistance to extinction compared with Fischer344 strain. In Lewis rats, THC exposure did not increse heroin CPP but potentiated the effect of heroin priming. In Fischer344 rats, THC exposure increased heroin CPP and made it resistant to extinction. Lewis rats showed marked seeking reactions during extinction and hedonic reactions in response to heroin priming. THC pre-exposure increased responding for iv heroin self-administration on FR3 and FR5 and on progressive ratio 3-4 in Lewis but not in Fisher344 rats. After extinction, presentation of discriminative stimuli associated to drug availability on the active nose-poke as well as priming by passive heroin exposure, reinstated responding more effectively in Lewis rats pre-exposed to THC than in saline controls. Conclusions: These observations suggest that, in genetically predisposed individuals, adolescent Cannabis exposure can increase vulnerability to heroin addiction by augmenting heroin reinforcing properties. These studies were founded by the Dipartimento politiche antidroga, Presidenza del Consiglio, Italy
Adolescent Cannabis exposure differentially affects Heroin Reinforcement and Accumbens Dopamine transmission in Lewis and Fisher344 rats
LECCA, DANIELE
2014-01-01
Abstract
Background: Vulnerability to drug addiction depends on acquired as well as genetic factors (Swendsen & Le Moal 2010). Among acquired factors is previous exposure to other drugs of abuse. Thus, exposure to Cannabis has been suggested to predispose to heroin abuse and dependence (Gateway Hypothesis) (Kandel et al. 2006). Here we studied the influence of adolescent delta 9-THC exposure on heroin reward and renforcement and on the in vivo dopamine stimulant properties of heroin in two inbred rat strains differentially vulnerable to drugs of abuse, the addiction prone Lewis and the addiction resistant Fisher344 strain. Results: THC increased extracellular DA, as estimated by microdialysis, in Lewis but not in Fischer 344 rats. Adolescent THC exposure potentiated DA stimulant effects of heroin in the shell and core of Lewis and only in the core of Fischer344 rats. Control Lewis rats developed stronger conditioned place preference (CPP) to heroin and resistance to extinction compared with Fischer344 strain. In Lewis rats, THC exposure did not increse heroin CPP but potentiated the effect of heroin priming. In Fischer344 rats, THC exposure increased heroin CPP and made it resistant to extinction. Lewis rats showed marked seeking reactions during extinction and hedonic reactions in response to heroin priming. THC pre-exposure increased responding for iv heroin self-administration on FR3 and FR5 and on progressive ratio 3-4 in Lewis but not in Fisher344 rats. After extinction, presentation of discriminative stimuli associated to drug availability on the active nose-poke as well as priming by passive heroin exposure, reinstated responding more effectively in Lewis rats pre-exposed to THC than in saline controls. Conclusions: These observations suggest that, in genetically predisposed individuals, adolescent Cannabis exposure can increase vulnerability to heroin addiction by augmenting heroin reinforcing properties. These studies were founded by the Dipartimento politiche antidroga, Presidenza del Consiglio, Italy
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