Changes in G-protein activity mediated through the stimulation of dopamine and GABA(B) receptors in the mesolimbic dopaminergic system of morphine-sensitized mice.

The behavioural sensitization has been recognized as the increased behavioural response and the undesirable long-lasting changes in brain functions after repeated administration of abuse drugs. We examined whether behavioural sensitization to hyperlocomotion induced by intermittent morphine treatment could result from any changes in dopamine and GABA(B) receptor functions to activate G-proteins in the brain rewarding system in mice. Intermittent morphine treatment results in the upregulation of dopamine receptor-regulated G-protein activation in the mouse limbic forebrain, whereas this treatment causes the downregulation of GABA(B) receptor function to activate G-protein in the mouse lower midbrain. In behavioural experiments, intermittent administration of morphine in combination with either a dopamine receptor antagonist haloperidol or a GABA(B) receptor agonist baclofen abolished the development of sensitization to morphine-induced hyperlocomotion. The present data provide evidence that these G-protein activation changes may lead to behavioural sensitization to morphine-induced hyperlocomotion in mice.