Muscarinic preferential M(1) receptor antagonists enhance the discriminative-stimulus effects of cocaine in rats.

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Tanda G, Katz JL

Muscarinic preferential M(1) receptor antagonists enhance the discriminative-stimulus effects of cocaine in rats.

Pharmacol Biochem Behav. 2007 Oct;87(4):400-4. Epub 2007 Jun 2.

PubMed ID

17631384 [ View in PubMed

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Abstract

Previous studies of benztropine analogues have found them to inhibit dopamine uptake like cocaine, but with less effectiveness than cocaine in producing behavioral effects related to drug abuse. Studies have assessed whether nonselective muscarinic antagonists decrease the effects of cocaine because many of the benztropine analogues are also muscarinic antagonists. As previous studies were conducted with nonselective muscarinic antagonists and the benztropine analogues show preferential affinity for the M(1) muscarinic receptor subtype, the present study examined interactions of cocaine and the preferential M(1) antagonists, telenzepine (TZP) and trihexyphenidyl (TXP) on subjective effects in rats trained to discriminate cocaine (10 mg/kg, i.p.) from saline injections. Cocaine dose-dependently increased the percentage of responses on the cocaine-appropriate lever, with full substitution at the training dose. In contrast neither TZP nor TXP produced more than 25% cocaine-appropriate responding at any dose. Both M(1) antagonists produced significant leftward shifts in the cocaine dose-effect curve, TZP at 3.0 and TXP at 0.3 and 1.0 mg/kg. The present results indicate that preferential antagonist actions at muscarinic M(1) receptors enhance rather than attenuate the discriminative-stimulus effects of cocaine, and thus those actions unlikely contribute to the reduced cocaine-like effects of BZT analogues.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Trihexyphenidyl	Muscarinic acetylcholine receptor M1	Protein	Humans	Yes	Antagonist	Details