A 5-HT(2C) receptor-mediated interaction between 2,5-dimethoxy-4-methylamphetamine and citalopram in the rat.
Justin R Eckler, Chad J Reissig, R A Rabin, Jerrold C Winter
Pharmacology, Biochemistry, and Behavior September 2004 DOI: 10.1016/j.pbb.2004.06.012 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Experimental study Peer reviewed |
|---|---|
| Sample size | 20 |
| Population | Rats |
| Interventions | Citalopram DOM WAY-100635 SB-242084 |
| Dose | DOM 0.6 mg/kg; 75 min pretreatment time |
| Topics | Serotonin |
| Key findings | Citalopram potentiates DOM-induced stimulus control via the 5-HT2C receptor, not through serotonin transporter blockade or 5-HT1A receptor activation. The 5-HT2C antagonist SB-242084 significantly blocked citalopram's effect, while the 5-HT1A antagonist WAY-100635 had no effect. |
Abstract
Previous studies conducted in our laboratory have shown that acute administration of the selective serotonin re-uptake inhibitor (SSRI), citalopram, potentiates the stimulus effects of the phenethylamine hallucinogen [-]-2,5-dimethoxy-4-methylamphetamine (DOM) in the rat while neither substituting for the DOM stimulus when administered alone nor altering brain levels of DOM. The present investigation was designed to determine the mechanism by which citalopram acts on DOM-induced stimulus control. To that end, we tested the following hypotheses: (a) citalopram blocks the transport of DOM by the serotonin transporter, (b) citalopram acts via the 5-HT(1A) receptor, and (c) citalopram acts via the 5-HT(2C) receptor. Hypothesis (a) was rejected on the basis of equilibrium saturation studies of [3H]citalopram binding, which revealed no significant affinity of DOM for the 5-HT transporter of rat brain membranes. Hypotheses (b) and (c) were tested in a group of 20 rats in which stimulus control was established with DOM (0.6 mg/kg; 75 min pretreatment time). A two-lever, fixed ratio 10 (FR10), positively reinforced task with saline controls was employed. Hypothesis (b), a role for the 5-HT(1A) receptor, was rejected on the basis of an absence of antagonism of the effects of citalopram on DOM by the selective 5-HT(1A) receptor antagonist, WAY-100635. In contrast, Hypothesis (c), a role for the 5-HT(2C) receptor, gained support from the observation of significant antagonism of the effects of citalopram on DOM by the selective 5-HT(2C) receptor antagonist, SB-242084.
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 8
- Psilocybin-induced stimulus control in the rat. Pharmacology, Biochemistry, and Behavior October 1, 2007
- Addressing the Current Knowledge and Gaps in Research SurroundingLysergic Acid Diethylamide (LSD), Psilocybin, and Psilocin in RodentModels Current Topics in Medicinal Chemistry July 6, 2023
- Head-twitch response in rodents induced by the hallucinogen 2,5-dimethoxy-4-iodoamphetamine: a comprehensive history, a re-evaluation of mechanisms, and its utility as a model. Drug Testing and Analysis April 19, 2012
- 5-HT_2A and 5-HT_2C Receptors Exert Opposing Effects on Locomotor Activity in Mice Neuropsychopharmacology July 1, 2009
- Hallucinogens as discriminative stimuli in animals: LSD, phenethylamines, and tryptamines. Psychopharmacology April 2009
and 3 more in the library
Cites 10
- The paradox of 5-methoxy-N,N-dimethyltryptamine: an indoleamine hallucinogen that induces stimulus control via 5-HT1A receptors. Pharmacology, Biochemistry, and Behavior 2000
- DOM (STP), a New Hallucinogenic Drug, and DOET: Effects in Normal Subjects American Journal of Psychiatry September 1, 1968
- The effects of acute and subchronic treatment with fluoxetine and citalopram on stimulus control by DOM. Pharmacology, Biochemistry, and Behavior December 2002
- Potentiation of DOM-induced stimulus control by fluoxetine and citalopram: role of pharmacokinetics. Life Sciences August 2, 2002
- A sensitive method for determining levels of [-]-2,5,-dimethoxy-4-methylamphetamine in the brain tissue. Journal of pharmacological and toxicological methods 2001
and 5 more in the library