enkephalin--ala(2)-mephe(4)-gly(5)- and Memory-Disorders

Learning/memory impairment is one of the most serious problems induced by stress, and the underlying mechanisms remain unclear. Opiates and opioid receptors are implicated in multiple physiological functions including learning and memory. However, there is no clear evidence whether the endogenous opioid system is involved in the formation of the stress-induced spatial reference memory impairment. The aim of the present study was to evaluate the role of μ opioid receptor in the stress-induced spatial reference memory impairment by means of Morris water maze (MWM) test in a mouse elevated platform stress model. The mice were trained in the MWM for four trials a session for 4 consecutive days after receiving the elevated platform stress, and intracerebroventricular injection of μ opioid receptor agonist DAMGO, antagonist CTAP or saline. Retention of the spatial training was assessed 24 h after the last training session with a 60-s free-swim probe trial using a new starting position. The results showed that intracerebroventricular injection of μ opioid receptor agonist DAMGO but not antagonist CTAP before MWM training impaired the memory retrieval of mice. Elevated platform stress before MWM training also impaired memory retrieval, which could be reversed by pre-injection of CTAP, and aggravated by DAMGO. These results suggest that endogenous opioid system may play a crucial role in the formation of the stress-induced memory impairment.

Topics: Animals; Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; Maze Learning; Memory Disorders; Mice; Receptors, Opioid, mu; Spatial Memory; Stress, Physiological

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.

Topics: Analgesics; Animals; Behavior, Animal; Drug Interactions; Dynorphins; Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; Enkephalins; Male; Memory; Memory Disorders; Mice; Mice, Inbred Strains; Peptide Fragments; Physostigmine; Receptors, Opioid, mu