The neurosteroid pregnenolone sulfate blocks deficits induced by a competitive NMDA antagonist in active avoidance and lever-press learning tasks in mice.
The neurosteroid pregnenolone sulfate (PREG-S) has been shown to modulate positively NMDA receptor activity and to have memory enhancing properties in mice. The present study was designed to evaluate the effects of post-training administration of PREG-S, alone or in combination with D-2-amino-5-phosphonovalerate (D-AP5), a competitive NMDA receptor antagonist, in Y-maze avoidance and appetitively motivated lever-press learning tasks and in a traction reflex test in mice. Intracerebroventricular (i.c.v.) administration of PREG-S (0.01-0.1 nmol/mouse) blocked the selective retention deficits induced by 0.02 nmol D-AP5 in the Y-maze avoidance task. PREG-S (0.1 nmol, i.c.v.) also blocked the retention deficits induced by 0.02 nmol D-AP5 in the lever-press task. Post-training administration of PREG-S alone (0.001-0.1 nmol, i.c.v.) had no effect on retention performance in the Y-maze and the lever-press tasks. PREG-S (1-10 nmol, i.c.v.) significantly reduced the impairment of the traction reflex induced by 2 nmol D-AP5. The ability of PREG-S to block retention performance deficits as well as motor impairment induced by D-AP5 is in agreement with its positive modulatory action at NMDA receptors.
Mathis
C
C
Laboratoire de Psychophysiologie, URA 1295 CNRS, Université Louis Pasteur, Strasbourg, France.
Vogel
E
E
Cagniard
B
B
Criscuolo
F
F
Ungerer
A
A
D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology; D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects*; D001667:Binding, Competitive / Q000187:drug effects; D003216:Conditioning, Operant / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D007276:Injections, Intraventricular; D008297:Male; D008568:Memory / Q000187:drug effects; D051379:Mice; D011284:Pregnenolone / Q000008:administration & dosage / Q000494:pharmacology*; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*; D012018:Reflex / Q000187:drug effects
D018691:Excitatory Amino Acid Antagonists; D016194:Receptors, N-Methyl-D-Aspartate; D011284:Pregnenolone; D015763:2-Amino-5-phosphonovalerate