alpha2-Adrenoceptor antagonists reverse the 5-HT2 receptor antagonist suppression of head-twitch behavior in mice.
Kinzo Matsumoto, Maho Mizowaki, S Thongpraditchote, Yukihisa Murakami, H Watanabe
Pharmacology, Biochemistry, and Behavior March 1997 DOI: 10.1016/s0091-3057(96)00223-7 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Experimental study Peer reviewed |
|---|---|
| Population | Mice |
| Interventions | Idazoxan Yohimbine Clonidine Ritanserin Ketanserin Prazosin 5-MeO-DMT 6-OHDA p-CPA Nomifensine |
| Dose | 5-MeO-DMT 16 mg/kg IP; clonidine 0.01 mg/kg IP; ritanserin 0.03 mg/kg IP; ketanserin 0.01 mg/kg IP; idazoxan 0.08-0.5 mg/kg IP; yohimbine 0.2-2.0 mg/kg IP; prazosin 1.25 mg/kg IP |
| Measures | head-twitch response |
| Topics | Serotonin |
| Key findings | Idazoxan and yohimbine attenuated the suppression of head-twitch responses by ritanserin and ketanserin, an effect reduced by noradrenaline depletion but not serotonin depletion. The authors propose that noradrenaline stimulation of alpha1-adrenoceptors is involved in this antagonism. |
Abstract
The alpha2-adrenoceptor agonist clonidine, as well as 5-HT2 receptor antagonists, reportedly suppress 5-HT2 receptor-mediated head-twitch behavior. We investigated the effect of alpha2-adrenoceptor antagonists on the suppressive action of 5-HT2 receptor antagonists in mice pretreated with the noradrenaline toxin 6-hydroxydopamine (6-OHDA) or the 5-HT synthesis inhibitor p-chlorophenylalanine (p-CPA). In normal mice, idazoxan (0.08-0.2 mg/kg, IP) or yohimbine (0.2-2.0 mg/kg, IP), both alpha2-adrenoceptor antagonists, had no effect on the head-twitch response caused by 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT; 16 mg/kg, IP), but idazoxan significantly enhanced the response at 0.5 mg/kg. On the other hand, these alpha2-adrenoceptor antagonists, at doses that had no effect on the basal number of head-twitches (idazoxan 0.2 mg/kg and yohimbine 0.5 mg/kg), significantly attenuated not only the suppressive effect of clonidine (0.01 mg/kg, IP) on head-twitch response but also that of the 5-HT2 receptor antagonist ritanserin (0.03 mg/kg, IP). Moreover, idazoxan (0.2 mg/kg) also significantly reversed the inhibition by 0.01 mg/kg (IP) ketanserin, a selective 5-HT2 receptor antagonist. Pretreatment with 6-OHDA plus nomifensine but not with p-CPA significantly attenuated the effect of idazoxan (0.2-0.5 mg/kg) on the ritanserin inhibition of the head-twitch response. Prazosin, an alpha1-adrenoceptor antagonist, dose-dependently suppressed the response, and the effect of prazosin (1.25 mg/kg) was significantly attenuated by 0.5 mg/kg idazoxan. These results indicate that endogenous noradrenaline is involved in the apparent antagonistic interaction between selective alpha2-adrenoceptor antagonists and 5-HT2 receptor antagonists in the head-twitch response, and suggest that noradrenaline stimulation of alpha1-adrenoceptors may be involved in this apparent antagonism.
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Citations in the library
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- Animal Models of Serotonergic Psychedelics ACS Chemical Neuroscience September 24, 2012
- Suppressive effect of mitragynine on the 5-methoxy-N,N-dimethyltryptamine-induced head-twitch response in mice. Pharmacology, Biochemistry, and Behavior 1997
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