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ReseaRch highlights

AddICtION against heroin?

Relapse after addictive- with- steadily self-administering heroin Drug-seeking behaviour has also drawal is a big societal problem by pressing a lever in a designated been linked to dysregulation of gluta- and is thought to be induced by chamber that contained a light as an mate and transmission. The environmental cues. The identifica- environmental cue did not change authors found that the expression tion of treatments that attenuate their heroin intake behaviour after of AMPA (α-amino-3-hydroxy- cue-induced relapse is one aim treatment with CBD. After 14 days 5-methyl-4-isoxazole propionic acid) of research. This study of drug abstinence, rats were GluR1 receptors, which are strongly showed that the non-psychotropic re-exposed to the self-administration linked to drug-seeking behaviour, component of cannabis, chamber and stimulus light cue or to was downregulated in the NAc core (CBD), antagonizes cue-induced the light cue alone. The drug-seeking and the medial and lateral shell in drug-seeking behaviour after heroin behaviour of rats that had been heroin-addicted rats. 24 hours after withdrawal and discovered that it treated with CBD 24 hours prior to CBD administration, GluR1 protein acts by normalizing glutamate and the behavioural test was attenuated. expression was normalized in the receptor expression It is noteworthy that during these NAc core and medial shell. levels in neurons that are involved in tests the rats did not have access to This study reveals unexpected the drug-seeking behaviour. heroin after lever pressing, as that properties of CBD, namely the The authors investigated the would have reinstated their drug selective and prolonged inhibition effect of CBD on the maintenance, dependence. The results suggest that of cue-induced drug seeking. These extinction and relapse of heroin CBD specifically attenuated drug- characteristics of CBD thus contrast seeking in rats. Animals which were seeking behaviour in response to with those of the other main con- environmental cues. stituent of cannabis, the psycho active The striatum is thought to be Δ9- (THC), involved in reward behaviour and which has been associated with addic- habit formation. The authors found tion vulnerability. CBD could therefore that mRNA and protein levels of the be exploited for the development of

cannabinoid receptor CB1R were to combat relapse. significantly increased in the Claudia Wiedemann mesolimbic system (specifically the nucleus accumbens (NAc) and dorsal ORIGINAL RESEARCH PAPER Ren, Y. et al. Cannabidiol, a nonpsychotropic component of striatum) of heroin-addicted rats but cannabis, inhibits cue-induced heroin seeking not in the dorsolateral division of the and normalizes discrete mesolimbic neuronal striatum (which receives primarily disturbances. J. Neurosci. 29, 14764–14769 (2009) FuRtHER REAdING Kauer, J. A. & Malenka, R. C. sensorimotor cortical input). CBD- Synaptic plasticity and addiction. Nature Rev. treated addicted rats had levels of Neurosci. 8, 844–858 (2007) | Murray, R. M., CB R similar to control animals. Morrison, P. D., Henquet, C. & Di Forti, M. 1 Cannabis, the mind and society: the hash These findings are consistent with realities. Nature Rev. Neurosci. 8, previous studies which showed 885–895 (2007) | Kalivas, P. W. The glutamate homeostasis hypothesis of addiction. Nature Rev. that inhibition of CB1R blocks Neurosci. 10, 561–572 (2009) cue-induced drug-seeking behaviour.

NATuRe RevIews | NeurosCieNCe voluMe 11 | jANuARy 2010