Chronic administration of the histamine H receptor agonist immepip decreases L-Dopa-induced dyskinesias in 6-hydroxydopamine-lesioned rats.

RATIONALE

Histamine H receptors (HRs) are co-expressed with dopamine D receptors (DRs) by striato-nigral medium spiny GABAergic neurons, where they functionally antagonize DR-mediated responses.

OBJECTIVES AND METHODS

We examined whether the chronic administration of the HR agonist immepip modifies dyskinesias induced by L-3,4-dihydroxyphenylalanine, L-Dopa (LIDs), in rats lesioned with 6-hydroxydopamine in the substantia nigra pars compacta, and the effect of DR and HR co-activation on glutamate and GABA content in dialysates from the dorsal striatum of naïve rats.

RESULTS

The systemic administration (i.p.) of L-Dopa for 14 days significantly increased axial, limb, and orolingual abnormal involuntary movements (AIMs) compared with the vehicle group. The chronic administration of the HR agonist immepip alongside L-Dopa significantly decreased axial, limb, and orolingual AIMs compared with L-Dopa alone, but AIMs returned to previous values on immepip withdrawal. Chronic immepip was ineffective when administered prior to L-Dopa. The chronic administration of immepip significantly decreased GABA and glutamate content in striatal dialysates, whereas the administration of L-Dopa alone increased GABA and glutamate content.

CONCLUSIONS

These results indicate that chronic HR activation reduces LIDs, and the effects on striatal GABA and glutamate release provide evidence for a functional interaction between DRs and HRs.