Influence of potassium channel modulators on morphine state-dependent memory of passive avoidance.
In a step-down passive avoidance task, the pre-training injection of 1.25-10 mg/kg of morphine impaired memory. This was restored when injection of the same dose of morphine (pre-test treatment) was repeated 24 h later (morphine state-dependent learning: morphine St-D). ATP-dependent potassium (K(ATP)) channels have been reported to be involved in several actions of morphine following mu-receptor stimulation. We have studied the effect of K(ATP) modulators and naloxone in the restoration of memory by morphine in mice. To investigate the part played by cholinergic systems in the effects of a K(ATP) antagonist (glibenclamide) on morphine St-D, we administered low doses of atropine before glibenclamide administration. Locomotor activity was also studied. Naloxone (0.06-1 mg/kg) reversed the effect of pre-test morphine administration. The effects of the K(ATP) channel blocker glibenclamide (2-18 mg/kg) were similar to those of the pre-test administration of morphine. Pre-test co-administration of glibenclamide and morphine showed no potentiation of the morphine effect. Glibenclamide alone or in combination with morphine did not affect locomotor activity. Pre-test administration of different doses of diazoxide (15-60 mg/kg), a K(ATP)-channel opener, had no effect on restoration of memory when used alone or in combination with morphine. In both cases, the locomotor activity was significantly reduced. Diazoxide blocked the effect of glibenclamide on memory recall. Low-dose atropine also prevented glibenclamide enhancement of memory recall, suggesting that this action of glibenclamide is through the cholinergic system.
Zarrindast
M R
MR
Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran. zarinmr@ams.ac.ir
Jafari
M R
MR
Shafaghi
B
B
Djahanguiri
B
B
D000255:Adenosine Triphosphate / Q000502:physiology; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D001362:Avoidance Learning / Q000187:drug effects*; D003981:Diazoxide / Q000494:pharmacology; D005905:Glyburide / Q000494:pharmacology; D008297:Male; D008568:Memory / Q000187:drug effects*; D051379:Mice; D009020:Morphine / Q000009:adverse effects*; D009043:Motor Activity / Q000187:drug effects; D009270:Naloxone / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D026902:Potassium Channel Blockers / Q000494:pharmacology; D015221:Potassium Channels / Q000819:agonists / Q000187:drug effects* / Q000502:physiology
D009292:Narcotic Antagonists; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D009270:Naloxone; D009020:Morphine; D001285:Atropine; D000255:Adenosine Triphosphate; D003981:Diazoxide; D005905:Glyburide