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, 182 (3), 393-9

Tolerance to the Procholinergic Action of the D1 Receptor Full Agonist Dihydrexidine

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Tolerance to the Procholinergic Action of the D1 Receptor Full Agonist Dihydrexidine

Mark R Wade et al. Psychopharmacology (Berl).

Abstract

Rationale: It has been well established that dopamine D1 receptor agonists increase acetylcholine (ACh) release in the brain, an effect that has been suggested to contribute to their procognitive properties.

Objectives: We sought to examine whether the ACh-releasing action of the D1 receptor full agonist dihydrexidine HCl (DHX) is altered after repeated administration.

Results: DHX dose-dependently (3, 9, 18, and 36 mg/kg, i.p.) increased ACh efflux in the hippocampus of freely moving rats through D1 receptor stimulation, as the D1 receptor antagonist SCH 23390 (0.3 mg/kg, i.p.) abolished the effect of DHX (18 mg/kg, i.p.). Daily injections of DHX (18 mg/kg, i.p.) over 14 days did not significantly affect basal hippocampal ACh concentrations, but they significantly curtailed the stimulatory action of a challenge injection of DHX (18 mg/kg, i.p.) on ACh efflux.

Conclusions: Tolerance to the procholinergic action of DHX develops with repeated administration.

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