The effect of MK-801 and other antagonists of NMDA-type glutamate receptors on brain-stimulation reward.
L J Herberg, I C Rose
Psychopharmacology 1989 DOI: 10.1007/bf00634458 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Preclinical animal study Peer reviewed |
|---|---|
| Population | Rats (variable-interval self-stimulation) |
| Interventions | MK-801 Ketamine HCl Kynurenic acid |
| Dose | MK-801 10-100 micrograms/kg IP (low doses) and 300 micrograms/kg IP (higher dose); Ketamine HCl 3.0-100 mg/kg IP; Kynurenic acid 3.0-300 mg/kg IP |
| Key points | Low doses of MK-801 and ketamine enhanced variable-interval self-stimulation responding, with MK-801 producing a more prolonged and broader dose-related facilitation than ketamine; a high MK-801 dose caused ataxia and disrupted responding. Kynurenic acid depressed responding. The authors argue the stimulant effects are intrinsic to selective NMDA antagonists and differ from those of dopamine-dependent stimulants. |
Abstract
MK-801 is a ligand at phencyclidine recognition sites associated with NMDA-coupled cation channels, where it acts as a potent noncompetitive antagonist of central glutamate/aspartate (NMDA-type) receptors. Low doses (10-100 micrograms/kg IP) produced a dose-related and prolonged (greater than 1 h) enhancement of variable-interval self-stimulation responding. Higher doses (300 micrograms/kg) caused flaccid ataxia and disrupted responding. Ketamine HCl (3.0-100 mg/kg IP), a dissociative anaesthetic binding to the phencyclidine site, produced a similar response pattern, but facilitation was less prolonged and occurred over a narrower dose range. Kynurenic acid (3.0-300 mg/kg IP), a nonselective competitive antagonist of glutamate receptors, produced only depression of responding, possibly the result of kynurenate-induced blockade of central kainate and/or quisqualate receptors. The behavioural stimulant effects of MK-801 appear to be an intrinsic and essential feature of selective NMDA antagonists, and these effects of MK-801 differ qualitatively and quantitatively from the well-known facilitatory effects of dopamine-dependent stimulants.