Potentiation of DOM-induced stimulus control by non-competitive NMDA antagonists: a link between the glutamatergic and serotonergic hypotheses of schizophrenia.
Jerrold C Winter, Mireille M Doat, R A Rabin
Life Sciences December 8, 2000 DOI: 10.1016/s0024-3205(00)00934-6 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Animal experiment Peer reviewed |
|---|---|
| Population | Rats |
| Interventions | DOM dizocilpine ketamine |
| Dose | DOM 0.6 mg/kg (training dose); DOM 0.1 mg/kg (fixed test dose); PCP 3 mg/kg |
| Topics | Serotonin |
| Key findings | Non-competitive NMDA antagonists potentiate the discriminative stimulus effects of DOM in rats. |
Abstract
The present investigation examined the interaction between 2,5-dimethoxy-4-methylamphetamine [DOM] and non-competitive NMDA antagonists in rats trained with DOM [0.6 mg/kg; 75 min pretreatment time] as a discriminative stimulus. Pretreatment with phencyclidine [PCP] at a dose of 3 mg/kg shifted the DOM dose-response relationship to the left. When a fixed dose of DOM [0.1 mg/kg] which by itself yielded 32% DOM-appropriate responding was combined with a range of doses of PCP, dizocilpine, and ketamine, DOM-appropriate percentages increased to maxima of 73%, 84%, and 79%, respectively. When given alone, PCP, dizocilpine, and ketamine were followed by maxima of 36%, 15%, and 13%, respectively. It is concluded that the effects of DOM as a discriminative stimulus are potentiated by pretreatment with non-competitive antagonists of glutamate receptors of the NMDA subtype. These data suggest that the application of the technique of drug-induced stimulus control may prove useful in the reconciliation and integration of current hypotheses as to the etiology of psychotic disorders.