Does dizocilpine (MK-801) selectively block the enhanced responsiveness to repeated amphetamine administration?
In order to examine the hypothesis that N-methyl-D-aspartate (NMDA) receptors are selectively involved in the development of stimulant sensitization, we characterized the interaction between acute and chronic dizocilpine (MK-801) + amphetamine using a detailed behavioral analysis, including concurrent assessment of the locomotor and stereotype components of the stimulant response and continuous monitoring of all the various phases of the emergent sensitization. The results showed that MK-801 (0.125 mg/kg) significantly affected the acute response to amphetamine (0.5, 1.75, 4.0 mg/kg), increasing or decreasing locomotor activity depending on dose. Repeated administration of MK-801 + amphetamine resulted in a suppression of stereotyped behaviors and a potentiated locomotor sensitization. These findings suggest that rather than blocking the development of sensitization, MK-801 pretreatment may produce a unique behavioral augmentation that is apparent during coadministration and that persists up to 48 hr in the response to amphetamine challenge.
Segal
D S
DS
Department of Psychiatry, School of Medicine, University of California, San Diego, La Jolla 92093, USA.
Kuczenski
R
R
Florin
S M
SM
D000661:Amphetamine / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D000818:Animals; D001143:Arousal / Q000187:drug effects*; D001921:Brain / Q000187:drug effects; D016291:Dizocilpine Maleate / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D008297:Male; D009043:Motor Activity / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects; D013239:Stereotyped Behavior / Q000187:drug effects
D016194:Receptors, N-Methyl-D-Aspartate; D016291:Dizocilpine Maleate; D000661:Amphetamine