Repeated administration of low doses of cocaine enhances the sensitivity of 5-HT2 receptor function.
N A Darmani, B R Martin, Richard A Glennon
Pharmacology, Biochemistry, and Behavior March 1, 1992 DOI: 10.1016/0091-3057(92)90367-o (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Animal experiment Peer reviewed |
|---|---|
| Population | Mice |
| Interventions | Cocaine 5-MeO-DMT DOI 8-OH-DPAT |
| Dose | 5-20 mg/kg |
| Duration | Up to 172 h following cessation of cocaine treatment |
| Topics | Serotonin |
| Citations | 48 |
| Key findings | Cocaine acutely inhibits the 5-MeO-DMT-induced head-twitch response in mice, while withdrawal from chronic cocaine treatment enhances the response, indicating serotonergic supersensitivity. |
Abstract
The acute and chronic effects of cocaine were evaluated on the 5-hydroxytryptamine (5-HT)-receptor 5-HT2 mediated behavioral function, the head-twitch response (HTR), in mice. In a recent study, we reported that the (+/-)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane HCl (DOI)-induced HTR was dose dependently reduced by cocaine via indirect stimulation of serotonergic 5-HT1A and adrenergic alpha 2 receptors. In the present investigation, the HTR was evoked by the nonselective 5-HT agonist 5-methoxy-N,N-dimethyltryptamine hydrogen oxolate (5-MeO-DMT). Cocaine by itself failed to produce HTR but dose dependently inhibited the 5-MeO-DMT-induced behavior. Cocaine's effects were not due to 5-HT3 antagonism since acute administration of the more potent 5-HT3 antagonist (ICS-205,930) failed to produce or modify the 5-MeO-DMT-induced behavior. During withdrawal from chronic cocaine treatment (5-20 mg/kg), 5-MeO-DMT-induced HTR was enhanced. Depending upon the cocaine dose used, the induced supersensitivity persisted up to 172 h following cessation of cocaine treatment. The mechanisms of cocaine-induced supersensitivity were further investigated using the more selective 5-HT2 agonist DOI. Withdrawal from a low-dose (0.03-1.25 mg/kg) chronic cocaine treatment caused the DOI-induced HTR to increase, whereas withdrawal from a 5- and 10-mg/kg cocaine regimen had no significant effect. The maximal effect persisted up to 36 h following termination of cocaine treatment. Relative to vehicle-exposed controls, withdrawal from cocaine treatment enhanced the inhibitory potency of the 5-HT1A agonist (+-)-8-hydroxy-2-(di-n-propylamino)tetralin HBr (8-OH-DPAT) on DOI-induced HTR.(ABSTRACT TRUNCATED AT 250 WORDS)
Comparable studies
Other preclinical and animal studies on serotonin, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Psilocybin induces rapid and persistent growth of dendritic spines in frontal cortex in vivo Mice | 2021 | Observational cohort | |
| Neurotoxicity of the psychedelic amphetamine, methylenedioxymethamphetamine. Rats (implied by typical neurochemical study context) | 1987 | Experimental study | |
| Psychedelics promote neuroplasticity through the activation of intracellular 5-HT2A receptors In vitro and in vivo (rodent) models | 2023 | Experimental study | |
| 3,4-Methylenedioxymethamphetamine and 3,4-methylenedioxyamphetamine destroy serotonin terminals in rat brain: quantification of neurodegeneration by measurement of [3H]paroxetine-labeled serotonin uptake sites. Rat brain | 1987 | Animal experiment | |
| Comparison of the monoamine transporters from human and mouse in their sensitivities to psychostimulant drugs Human and mouse dopamine, norepinephrine, and serotonin transporters expressed in cells | 2006 | In vitro laboratory study |
Citations in the library
Cited by 2
- The psychedelic (-)-2,5-dimethoxy-4-iodoamphetamine [(-)-DOI] demonstrates efficacy in reducing cocaine reward and motivation in male rats. Psychopharmacology August 1, 2025
- Serotonin Transporter Blockade Reduces the Psychedelic-Like Effects of 4-Methoxy- N -methyl- N -isopropyltryptamine and Related Analogs ACS Chemical Neuroscience May 27, 2026