Abstract
The effects of i.c.v. injection of the mu-selective opioid receptor agonist DAMGO and the effects of its combination with the endogenous kappa-opioid receptor agonist dynorphin A-(1-13) on memory processes were examined in mice, using spontaneous alternation performance associated with working memory in a Y-maze. DAMGO (10 and/or 30 ng) impaired spontaneous alternation performance and increased total arm entries, which are considered to reflect locomotor activity. beta-Funaltrexamine (5 micrograms, i.c.v.), a mu-selective opioid receptor antagonist, almost completely antagonized the impairment of alternation performance induced by DAMGO (10 ng). Physostigmine (0.1 mg/kg, i.p.), a cholinesterase inhibitor, improved the DAMGO (10 ng)-induced impairment of alternation performance. Dynorphin A-(1-13) (1, 3 and 10 micrograms, i.c.v.) alone was without significant effects on alternation performance. On the other hand, dynorphin A-(1-13) (3 and 10 micrograms) significantly improved the impairment of spontaneous alternation performance induced by DAMGO (10 ng). The effects of dynorphin A-(1-13) (3 micrograms) on the DAMGO-induced impairment of spontaneous alternation were almost completely reversed by pretreatment with nor-binaltorphimine (4 micrograms, i.c.v.), a kappa-selective opioid receptor antagonist. The present results demonstrate that DAMGO impairs alternation performance by activating mu-opioid receptors, whereas dynorphin A-(1-13) attenuates the DAMGO-induced impairment of alternation performance through the mediation of kappa-opioid receptors. These findings suggest that mu- and kappa-opioid systems are fully involved in memory function and have opposite effects on spontaneous alternation performance as it is reflected by working memory in mice.
JPET articles become freely available 12 months after publication, and remain freely available for 5 years.Non-open access articles that fall outside this five year window are available only to institutional subscribers and current ASPET members, or through the article purchase feature at the bottom of the page.
|