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Updated: Aug 11, 2026
Elevated Plus Maze for Mice
Published on: December 22, 2008
Evidence that mCPP-induced anxiety in the plus-maze is mediated by postsynaptic 5-HT2C receptors but not by
E L Gibson1, A M Barnfield, G Curzon
1Department of Neurochemistry, Institute of Neurology, London, U.K.
Abstract:
1-(3-Chlorophenyl)piperazine (mCPP) (0.125-1.0 mg/kg i.p.), previously shown to inhibit social interaction, dose-dependently reduced exploration of the open arms of an elevated plus-maze. These findings suggest anxiogenic properties. The effect of mCPP was more potently inhibited by 1-(1-naphthyl)piperazine than by ketanserin, indicative of its mediation via activation of 5-HT2C rather than 5-HT2A receptors. The 5-HT1B receptor agonist CGS 12066B did not antagonise the anxiety-like response to mCPP, and further reduced exploration at the highest dose tested (10 mg/kg i.p.). Depletion of serotonin (5-HT) by p-chlorophenylalanine (PCPA, 150 mg/kg/day x 3) did not prevent the response, although PCPA itself increased open arm exploration. The 5-HT1A/B and beta-adrenoceptor antagonist 1-propanolol (5 mg/kg i.p.) and the peripheral beta 1-receptor antagonist atenolol (20 mg/kg i.p.) showed no significant activity on the plus-maze either alone or against the anxiogenic effect of mCPP. These results indicate that mCPP induces anxiety in the rat in the elevated plus-maze primarily by stimulation of postsynaptic 5-HT2C receptors, and suggest that sympathomimetic effects of mCPP are not involved.
Insights
1-(3-Chlorophenyl)piperazine (mCPP) induces anxiety-like behaviors in rats by activating serotonin 5-HT2C receptors. This effect is not mediated by serotonin depletion or beta-adrenoceptors.
Area of Science:
- Neuroscience
- Pharmacology
- Behavioral Science
Background:
- 1-(3-Chlorophenyl)piperazine (mCPP) is known to inhibit social interaction.
- Previous research suggests mCPP may have psychoactive properties.
Purpose of the Study:
- To investigate the anxiogenic effects of mCPP in rats using the elevated plus-maze.
- To determine the specific serotonin receptor subtypes involved in mCPP-induced anxiety-like behavior.
Main Methods:
- Rats were administered varying doses of mCPP (0.125-1.0 mg/kg i.p.).
- The effects of mCPP were assessed by measuring exploration of the open arms of an elevated plus-maze.
- Specific receptor antagonists and serotonin depletion were used to elucidate the mechanism of action.
Main Results:
- mCPP dose-dependently reduced exploration of the open arms, indicating anxiogenic properties.
- The anxiogenic effect of mCPP was more potently inhibited by 1-(1-naphthyl)piperazine than ketanserin, suggesting 5-HT2C receptor mediation.
- Serotonin depletion with PCPA did not prevent the response, and other receptor antagonists showed no significant activity.
Conclusions:
- mCPP induces anxiety in rats primarily through the stimulation of postsynaptic 5-HT2C receptors.
- Sympathomimetic effects of mCPP are unlikely to be involved in its anxiogenic action.
- The findings contribute to understanding the role of serotonin receptors in anxiety regulation.
