Memory facilitation by post-training intraperitoneal, intracerebroventricular and intra-amygdala injection of Ro 5-4864.
Post-training i.p. (2.0 or 5.0 mg/kg), i.c.v. (2.5 micrograms/rat), or intra-amygdala (1.6-40 ng/amygdala) administration of Ro 5-4864 causes memory facilitation of step-down inhibitory avoidance in rats. The effect is expressed as an increased latency to step down in a retention test carried out 24 h after training. Ro 5-4864 is a blocker of the Cl(-)-channel associated with GABAA receptors, at a site sensitive to the antagonist, PK11195, and different from that sensitive to picrotoxin. PK11195, given i.c.v. (2.5 micrograms/rat) or into the amygdala (8 ng/amygdala), antagonized the effect of Ro 5-4864. Intra-amygdala picrotoxin administration (80 ng/amygdala) also caused retrograde memory facilitation, but its effect was not antagonized by PK11195. At a higher dose (40 ng/amygdala), PK11195 had an amnestic effect of its own, which suggests that it might be acting against an endogenous ligand of receptor to Ro 5-4864 in the Cl(-)-channel. These findings support the hypothesis that there is a GABAA mechanism in the amygdala normally involved in the modulation of the post-training memory processing of aversive learnings.
Da Cunha
C
C
Departamento de Bioquimica, Instituto de Biociencias, U.F.R.G.S. (centro), Porto Alegre, RS Brazil.
Huang
C H
CH
Walz
R
R
Dias
M
M
Koya
R
R
Bianchin
M
M
Pereira
M E
ME
Izquierdo
I
I
Medina
J H
JH
D000679:Amygdala / Q000187:drug effects / Q000502:physiology*; D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects*; D001570:Benzodiazepinones / Q000008:administration & dosage / Q000494:pharmacology*; D002552:Cerebral Ventricles / Q000187:drug effects / Q000502:physiology*; D003292:Convulsants / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004597:Electroshock; D007274:Injections, Intraperitoneal; D007276:Injections, Intraventricular; D007546:Isoquinolines / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D008568:Memory / Q000187:drug effects*; D008845:Microinjections; D051381:Rats; D011919:Rats, Inbred Strains
D001570:Benzodiazepinones; D003292:Convulsants; D007546:Isoquinolines; C028513:4'-chlorodiazepam; C037850:PK 11195