ABSTRACT
To investigate the interaction between hippocampal γ-aminobutyric acid GABAA receptor (GABAAR) or GABAB receptor (GABABR) and N-methyl-D-aspartate receptor (NMDAR) in the acquisition of passive avoidance memory in rats, we used GABAA or GABAB agents, D-AP5 (as a NMDAR antagonist), and a combination of the mentioned drugs in a step-through task. All agents were microinjected into the intra-CA1 regions at a volume of 1⯵l/rat, prior to training. GABAAR agonist muscimol (0.2⯵g/rat), selective GABABR agonist baclofen (0.5⯵g/rat) or NMDAR antagonist D-AP5 (0.25⯵g/rat) decreased step-through latency, indicating a memory retention impairment. Neither GABAAR antagonist bicuculline (0.0625-0.25⯵g/rat) nor GABABR antagonist phaclofen (0.1-0.5⯵g/rat) altered memory retrieval by itself. Moreover, the lower dose of muscimol (0.05⯵g/rat) decreased D-AP5 (0.125⯵g/rat) response on memory acquisition, but bicuculline did not alter the D-AP5 response. Furthermore, baclofen and phaclofen at the dose of 0.1⯵g/rat potentiated D-AP5 response at the doses of 0.0625 and 0.125⯵g/rat, but abolished memory impairment induced by D-AP5 at the higher dose (0.25⯵g/rat). The results suggest that the microinjection of GABAA and GABAB agents into the CA1 region differently affects memory acquisition deficit induced by D-AP5. The activation of GABAARs increased the impairment effect of D-AP5 on passive avoidance memory, but their blockade did not have an effect. Also, the activation or blockade of GABABRs induced a similar and dual effect.
Subject(s)
Avoidance Learning/drug effects , Memory Disorders/metabolism , Receptors, GABA/drug effects , Receptors, GABA/metabolism , 2-Amino-5-phosphonovalerate/pharmacology , Animals , Baclofen/analogs & derivatives , Baclofen/pharmacology , Bicuculline/pharmacology , GABA-A Receptor Agonists/pharmacology , GABA-A Receptor Antagonists/pharmacology , GABA-B Receptor Agonists/pharmacology , GABA-B Receptor Antagonists/pharmacology , Hippocampus/drug effects , Male , Memory/physiology , Muscimol/pharmacology , Rats , Rats, Wistar , Receptors, GABA-B/drug effects , Receptors, GABA-B/metabolism , Receptors, N-Methyl-D-Aspartate/antagonists & inhibitors , gamma-Aminobutyric Acid/pharmacologyABSTRACT
In the present study, effects of the serotonergic system of the dorsal hippocampus (CA1) on harmaline-induced amnesia were examined. A single-trial step-down passive avoidance task was used for the assessment of memory retention in adult male NMRI mice. Pre-training intra-peritoneal (i.p.) administration of harmaline (1mg/kg) induced impairment of memory retention. Moreover, intra-CA1 administration of 5-HT1B/1D receptor agonist, CP94253 (5 ng/mouse), 5-HT1B/1D receptor antagonist, GR127935 (0.05 and 0.5 ng/mouse), 5-HT2A/2B/2C receptor agonist, α-methyl 5-HT (0.5 ng/mouse) and 5-HT2 receptor antagonist, cinancerine (0.5 ng/mouse) impaired memory acquisition, but did not affect locomotor activity and tail flick. Furthermore, pre-training intra-CA1 injection of subthreshold dose of CP94253 (0.05 ng/mouse) or GR127935 (0.005 ng/mouse) reversed impairment of memory acquisition induced by harmaline (1 mg/kg, i.p.). However, pre-training intra-CA1 infusion of subthreshold dose of α-methyl 5-HT (0.005 ng/mouse) or cinancerine (0.005 ng/mouse) with the administration of harmaline (0.5 and 1 mg/kg, i.p.) heighten impairment of memory acquisition. These findings implicate the involvement of CA1 serotonergic mechanism in harmaline-induced impairment of memory acquisition.
