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Chronic administration of the histamine H 3 receptor agonist immepip decreases L-Dopa-induced dyskinesias in 6-hydroxydopamine-lesioned rats.

Psychopharmacology 2019 Februrary 15
RATIONALE: Histamine H3 receptors (H3 Rs) are co-expressed with dopamine D1 receptors (D1 Rs) by striato-nigral medium spiny GABAergic neurons, where they functionally antagonize D1 R-mediated responses.

OBJECTIVES AND METHODS: We examined whether the chronic administration of the H3 R 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 D1 R and H3 R 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 H3 R 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 H3 R activation reduces LIDs, and the effects on striatal GABA and glutamate release provide evidence for a functional interaction between D1 Rs and H3 Rs.

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