Effect of the GABAergic system on memory formation and state-dependent learning induced by morphine in rats.
In the present study, the effects of intraperitoneal injections of GABA(A) receptor agonist and antagonist on memory formation and morphine state-dependent learning were investigated in rats. Pre-training administration of morphine (1-15 mg/kg) in a step-down passive avoidance task induced state-dependent learning with impaired memory retrieval on the test day. The impairment of memory was restored after the pre-test administration of the same dose of morphine. The pre-test administration of the GABA(A) receptor agonist, muscimol (0.01, 0.05 and 0.1 mg/kg), significantly decreased state-dependent retrieval induced by pre-test morphine (5 mg/kg). The state-dependency effect of morphine (1 mg/kg) was significantly potentiated by the pre-test administration of the GABA(A) receptor antagonist, bicuculline (0.125, 0.25 and 0.5 mg/kg). Furthermore, the pre-training injection of muscimol (0.01 mg/kg) impaired memory retrieval which was restored by pre-test morphine (1, 3 and 5 mg/kg) administration. However, the pre-training administration of bicuculline did not affect retention by itself. In addition, amnesia induced by pre-training morphine (5 mg/kg) was significantly reversed in rats which had received pre-test injections of muscimol (0.01, 0.05 and 0.1 mg/kg). Pre-test injections of bicuculline (0.125, 0.25 and 0.5 mg/kg) significantly decreased morphine-induced amnesia. It is concluded that the GABA(A) receptor mechanisms may be involved in the memory formation and it is postulated that these receptors may play an important role in morphine state-dependent learning.
Zarrindast
Mohammad-Reza
MR
Department of Pharmacology and Iranian National Center for Addiction Studies, School of Medicine, Tehran University of Medical Sciences, PO Box 13145-784, Tehran, Iran. zarinmr@ams.ac.ir
Noorbakhshnia
Maryam
M
Motamedi
Freshteh
F
Haeri-Rohani
Ali
A
Rezayof
Ameneh
A
D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects; D001640:Bicuculline / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D058785:GABA-A Receptor Agonists; D058787:GABA-A Receptor Antagonists; D007858:Learning / Q000187:drug effects*; D008297:Male; D008568:Memory / Q000187:drug effects*; D009020:Morphine / Q000494:pharmacology*; D009118:Muscimol / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D011963:Receptors, GABA-A / Q000502:physiology*
D058785:GABA-A Receptor Agonists; D058787:GABA-A Receptor Antagonists; D011963:Receptors, GABA-A; D009118:Muscimol; D009020:Morphine; D001640:Bicuculline