Inhibition of morphine-induced amnesia in morphine-sensitized mice: involvement of dorsal hippocampal GABAergic receptors.
In the present study, the effects of bilateral injections of the GABAergic receptor agents into the dorsal hippocampal CA1 regions (intra-CA1) on morphine-induced amnesia were examined in morphine sensitized-mice. Pre-training subcutaneous (s.c.) administration of morphine (5 mg/kg) suppressed the learning of a one-trial passive avoidance task. Amnesia induced by pre-training morphine was significantly reversed in mice which had previously received once daily injections of morphine (20 and 30 mg/kg, s.c.) for 3 days, which may be due to behavioral sensitization. Intra-CA1 injections of GABAA receptor agonist, muscimol (0.125, 0.25, 0.5 and 1 microg/mouse) or the GABAB receptor agonist, baclofen (1, 1.5 and 2 microg/mouse) prior to injection of morphine (20 mg/kg per dayx3 days) decreased the reversion of morphine-induced amnesia in morphine sensitized-mice. Daily intra-CA1 injections of muscimol or baclofen plus saline for 3 days did not alter memory formation. Furthermore, during development of sensitization, the combination of GABAA receptor antagonist, bicuculline (0.25, 0.5, 1 and 2 microg/mouse) with an ineffective dose of morphine (5 mg/kg, s.c.) reversed the amnesia induced by pre-training morphine. However, the same treatment with GABAB receptor antagonist, CGP35348 (2.5-40 microg/mouse) had no effect on the morphine response. On the other hand, daily intra-CA1 injections of bicuculline or CGP35348 alone for 3 days did not alter the amnesia induced by pre-training injection of morphine. The results suggest that morphine sensitization reverses the impairment of memory induced by morphine and that GABAergic receptors of the dorsal hippocampus may play an important role in this effect.
Zarrindast
Mohammad-Reza
MR
Department of Pharmacology, School of Medicine, and Iranian National Center for Addiction Studies, Tehran University of Medical Sciences, Tehran, Iran. zarinmr@ams.ac.ir
Hoghooghi
Vahid
V
Rezayof
Ameneh
A
D000647:Amnesia / Q000139:chemically induced / Q000473:pathology / Q000523:psychology; D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects; D001522:Behavior, Animal; D004334:Drug Administration Schedule; D004347:Drug Interactions; D018682:GABA Agents / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D007266:Inhibition, Psychological; D008297:Male; D051379:Mice; D009020:Morphine; D011930:Reaction Time / Q000187:drug effects; D018079:Receptors, GABA / Q000502:physiology*
D018682:GABA Agents; D018079:Receptors, GABA; D009020:Morphine