Targeted disruption of the cnrl gene (Ledent et al. 1999; Mascia et al. 1999) has been described. The marked similarities between opioid and cannabinoid receptor responses led to an investigation of the effects of morphine in CB1 receptor knockout mice. The results of these studies were that CB1 receptors appeared to regulate mesolimbic dopaminergic transmission in the nucleus accumbens which is believed to be involved in the reinforcing effects of morphine. Furthermore, while in vivo the acute effects of opiates in CB1 deficient mice were unaffected, the reinforcing properties and severity of the withdrawal syndrome were strongly reduced.
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