Receptor subtypes in opioid and stimulant reward

Studies of the behaviourally-reinforcing actions of opioid and stimulant drugs of abuse are reviewed in an attempt to identify their reward-related brain receptors. We focus on data generated by drug self-administration, brain stimulation reinforcement, and conditioned place preference paradigms. A consistent body of evidence supports a role for mu and delta, but not kappa, receptors in opioid reward. Stimulant reward apparently involves both D1 and D2 receptors; the data favour D2 mediation of stimulant drug reinforcement with a permissive or modulatory role for D1 receptors. The reward-relevant opioid and dopamine receptors, as well as the cannabinoid (marijuana) receptor, share the ability to couple Gi proteins that mediate inhibition of adenylate cyclase and stimulation of K+ conductance. These signal transduction mechanisms thus may be generally implicated in the reinforcing properties of diverse drugs of abuse.