D-cycloserine, a positive modulator of the N-methyl-D-aspartate receptor, enhances performance of learning tasks in rats.
Glycine has recently been shown to positively modulate the N-methyl-D-aspartate (NMDA) subclass of acidic amino acid receptors which are important in neural pathways involved in learning and memory. We report that d-cycloserine (DCS), an antimycobacterial agent known to cross the blood-brain barrier, binds with high affinity to this glycine modulatory site, functions as a positive modulator, and facilitates performance of learning tasks in rats. In addition, DCS appears to be a potent cognitive enhancer at doses lower than those required for antibacterial activity. Based on these data, we propose that modulation of NMDA receptors via glycinergic mechanisms may be a means of influencing cognitive processes.
Monahan
J B
JB
CNS Diseases Research, G.D. Searle Company, St. Louis, MO 63198.
Handelmann
G E
GE
Hood
W F
WF
Cordi
A A
AA
D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001362:Avoidance Learning / Q000187:drug effects; D003523:Cycloserine / Q000494:pharmacology*; D007858:Learning / Q000187:drug effects*; D008297:Male; D051381:Rats; D016194:Receptors, N-Methyl-D-Aspartate; D017981:Receptors, Neurotransmitter / Q000187:drug effects / Q000502:physiology*
D000900:Anti-Bacterial Agents; D016194:Receptors, N-Methyl-D-Aspartate; D017981:Receptors, Neurotransmitter; D003523:Cycloserine