M100907, a selective 5-HT(2A) receptor antagonist, attenuates phencyclidine-induced Fos expression in discrete regions of rat brain.
T Habara, T Hamamura, M Miki, K Ohashi, S Kuroda
European Journal of Pharmacology April 13, 2001 DOI: 10.1016/s0014-2999(01)00926-8 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Experimental study Peer reviewed |
|---|---|
| Population | Rat brain |
| Interventions | M100907 Phencyclidine (PCP) |
| Dose | M100907 0.5 mg/kg s.c.; PCP 5 mg/kg s.c. |
| Measures | Fos expression |
| Topics | Serotonin |
| Key findings | M100907 attenuated PCP-induced Fos expression in the nucleus accumbens core, shell, agranular insular cortex, and piriform cortex, but not in other regions. |
Abstract
5-HT and dopamine receptor antagonists have become widely used as atypical antipsychotics. Although 5-HT(2A) receptor antagonistic activity is thought to contribute to the atypical aspects of these agents, the precise mechanism remains unknown. M100907 (R(+)-alpha(2,3-dimethoxyphenyl)-1-[2(4-fluorophenyl)ethyl)]-4-piperidine -methanol), a selective 5-HT(2A) receptor antagonist, is reported to attenuate phencyclidine (PCP)-induced locomotion in rodents. For the purpose of identifying regions in which M100907 exerts its effect, we investigated the effects of M100907 on PCP-induced Fos expression in rat brain. PCP (5 mg/kg, subcutaneously, s.c.) induced Fos expression in the cingulate cortex area 3, the agranular insular cortex, the piriform cortex, the nucleus accumbens, the anterior paraventricular thalamic nucleus and the ventral lateral septal nucleus. Pretreatment with M100907 (0.5 mg/kg, s.c.) attenuated Fos expression induced by PCP in the nucleus accumbens core, the shell, the agranular insular cortex and the piriform cortex. M100907 did not induce Fos expression in any of the regions investigated including the dorsolateral caudate/putamen when given alone. These results indicate that 5-HT(2A) receptor antagonism attenuates Fos expression in a regionally specific manner in rat brain in the PCP model of psychosis.
Comparable studies
Other experimental studies on serotonin, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Psilocybin induces schizophrenia-like psychosis in humans via a serotonin-2 agonist action Healthy human volunteers | 1998 | Experimental study | |
| Amphetamine-type central nervous system stimulants release norepinephrine more potently than they release dopamine and serotonin | 2000 | Experimental study | |
| Methylenedioxyamphetamine (MDA) and methylenedioxymethamphetamine (MDMA) cause selective ablation of serotonergic axon terminals in forebrain: immunocytochemical evidence for neurotoxicity Rat brain | 1988 | Experimental study | |
| The molecular mechanism of "ecstasy" [3,4-methylenedioxy-methamphetamine (MDMA)]: serotonin transporters are targets for MDMA-induced serotonin release. Human platelet plasma membrane vesicles and bovine adrenal chromaffin granule membrane... | 1992 | Laboratory study | |
| 5-HT2AReceptor-Mediated Regulation of Brain-Derived Neurotrophic Factor mRNA in the Hippocampus and the Neocortex Rat brain | 1997 | Experimental study |
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- Antagonism of phencyclidine-induced stimulus control in the rat by other psychoactive drugs. Pharmacology, Biochemistry, and Behavior January 2008
- Do NMDA receptor antagonist models of schizophrenia predict the clinical efficacy of antipsychotic drugs? Journal of Psychopharmacology May 1, 2007
- Integrative role for serotonergic and glutamatergic receptor mechanisms in the action of NMDA antagonists: potential relationships to antipsychotic drug actions on NMDA antagonist responsiveness. Neuroscience and biobehavioral reviews June 2002
- Effects of the adenosine A(1) receptor agonist N(6)-cyclopentyladenosine on phencyclidine-induced behavior and expression of the immediate-early genes in the discrete brain regions of rats. Brain research. Molecular brain research April 30, 2002
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