Research reportDopamine is differentially involved in the locomotor hyperactivity produced by manipulations of opioid, GABA and glutamate receptors in the median raphe nucleus

- We studied effects of haloperidol on median raphe nucleus (MR) induced-hyperactivity.
- Glutamate antagonist pBB-PZDA in MR induced haloperidol insensitive hyperactivity.
- GABA agonists muscimol and baclofen induced haloperidol insensitive hyperactivity.
- Opioid agonists DAMGO and DPDPE induced haloperidol sensitive hyperactivity.
- The effects of different drugs injected in MR are mediated through different pathways.

The median raphe nucleus (MR) has been shown to exert a powerful influence on behavioral arousal and marked locomotor hyperactivity can be produced by intra-MR injections of a variety of drugs including GABAA and GABAB agonists, excitatory amino acid antagonists, and μ- and δ-opioid agonists. Other studies have indicated that the MR exerts an inhibitory influence on ascending dopamine systems, suggesting that MR induced alterations in activity may be mediated through changes in dopaminergic transmission. In the present study, we explored this possibility by examining whether systemic administration of the preferential D2 dopamine antagonist haloperidol is able to antagonize the hyperactivity produced by intra-MR injections of various drugs. We found that haloperidol completely blocked the locomotor response to intra-MR injections of the μ-opioid receptor agonist DAMGO and the δ-opioid receptor agonist DPDPE. In marked contrast, at doses which abolished the locomotor response to systemic amphetamine, haloperidol had no effect on the hyperactivity induced by intra-MR injections of GABAA agonist muscimol, the GABAB agonist baclofen, or the kainate/quisqualate antagonist pBB-PZDA, even though it suppressed baseline activity in these same animals. These results indicate that there must be at least two mechanisms capable of influencing behavioral arousal within the MR region, one of which is dependent on D2 dopamine receptors and the other is not.