Interactions of clozapine with the stimulus effects of DOM and LSD.
Pharmacology, Biochemistry, and Behavior September 1994 DOI: 10.1016/0091-3057(94)90464-2 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Animal drug discrimination study Peer reviewed |
|---|---|
| Population | Rats trained in a two-lever drug discrimination task |
| Interventions | 2 5-dimethoxy-4-methylamphetamine (DOM) lysergic acid diethylamide (LSD) clozapine atropine |
| Dose | 0.3, 1, 2, and 3 mg/kg clozapine; 3 and 4 mg/kg clozapine; 3 and 5 mg/kg atropine; 2 mg/kg clozapine combined with 3 mg/kg atropine |
| Topics | LSD |
| Key points | Clozapine partially antagonized the discriminative stimulus effects of DOM (0.3, 1, 2 mg/kg) and LSD (3, 4 mg/kg), with full antagonism of DOM at 3 mg/kg, while neither drug fully generalized to clozapine. Atropine at 3 mg/kg partially generalized to and partially attenuated the DOM cue, and the authors conclude an antimuscarinic component in clozapine's attenuation cannot be excluded. |
Abstract
Two groups of rats were trained with the 5-HT2 agonists 2,5-dimethoxy-4-methylamphetamine (DOM) or lysergic acid diethylamide (LSD) in a two-lever discrimination task. Tests of generalization and antagonism were then carried out with clozapine. DOM did not generalize to clozapine. Partial antagonism of DOM was observed with 0.3, 1, and 2 mg/kg clozapine and statistically significant full antagonism with 3 mg/kg. LSD did not fully generalize to clozapine. Partial antagonism of LSD was observed with 3 and 4 mg/kg clozapine. Because clozapine is known to block muscarinic as well as 5-HT2 receptors, atropine was studied in DOM-trained rats. DOM partially generalized to 3 mg/kg atropine. Partial attenuation of DOM stimulus effects was observed with 3 mg/kg atropine, and no attenuation with 5 mg/kg. A combination of 2 mg/kg clozapine and 3 mg/kg atropine vs. DOM produced response suppression in five of seven rats. The atropine test results do not exclude the possibility of an antimuscarinic component in the observed attenuation of DOM and LSD stimulus effects by clozapine.
Comparable studies
Other preclinical and animal studies on LSD, most cited first.
Citations in the library
Cited by 3
- The 5-HT1A receptor and the stimulus effects of LSD in the rat. Psychopharmacology October 2005
- The interactions of typical and atypical antipsychotics with the (-)2, 5,-dimethoxy-4-methamphetamine (DOM) discriminative stimulus. Neuropharmacology October 1995
- The time-dependent stimulus effects of R(-)-2,5-dimethoxy-4-methamphetamine (DOM): implications for drug-induced stimulus control as a method for the study of hallucinogenic agents. Psychopharmacology May 1995
Cites 10
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- Stimulus effects of ibogaine in rats trained with yohimbine, DOM, or LSD. Pharmacology, Biochemistry, and Behavior December 1, 1992
- Interactions between serotonergic agonists and antagonists in rats trained with LSD as a discriminative stimulus. Pharmacology, Biochemistry, and Behavior July 1988
- Potency of antipsychotics in reversing the effects of a hallucinogenic drug on locus coeruleus neurons correlates with 5-HT2 binding affinity. Neuropsychopharmacology May 1988
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