kappa-Opioid receptor agonists improve pirenzepine-induced disturbance of spontaneous alternation performance in the mouse.

We investigated the effects of kappa-opioid receptor agonists such as dynorphin A-(1-13) and U-50,488H on the muscarinic M1-selective receptor antagonist pirenzepine (3 micrograms, i.c.v.)-induced impairment of spontaneous alternation performance in the mouse. Although dynorphin A-(1-13)(1-5.6 micrograms, i.c.v.) or U-50,488H ((+/-)trans-3,4-dichloro-N-methyl-N-[2-(1-pyrrolidinyl)-cyclohexyl]- benzeneacetamide, methanesulfonate hydrate) (0.1-1 mg/kg, i.p.) alone did not influence either spontaneous alternation performance or total arm entries, pirenzepine (3 micrograms, i.c.v.) impaired spontaneous alternation performance without producing any significant change in total arm entries. In contrast, dynorphin A-(1-13) (3 and 5.6 micrograms, i.c.v.) and U-50,488H (0.3 and 1 mg/kg, i.p.) ameliorated the pirenzepine (3 micrograms, i.c.v.)-induced impairment of spontaneous alternation performance. The ameliorating effects of dynorphin A-(1-13)(3 micrograms, i.c.v.) and U-50,488H (0.3 mg/kg, i.p.) were almost completely reversed by pretreatment with nor-binaltorphimine (4 micrograms, i.c.v.), a kappa-opioid receptor antagonist. These results suggest that the stimulation of kappa-opioid receptors improves memory dysfunctions resulting from the blockade of muscarinic M1 receptors.