Characterization of a novel effect of serotonin 5-HT1A and 5-HT2A receptors: increasing cGMP levels in rat frontal cortex.
Meredith J. Regina, Jerrold C Winter, Richard A. Rabin
Neuropharmacology December 2003 DOI: 10.1016/s0028-3908(03)00287-9 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Laboratory study Peer reviewed |
|---|---|
| Population | Rat frontal cortical slices |
| Interventions | Serotonin DOM DPAT pirenperone MDL100907 SB242084 WAY100635 |
| Measures | cGMP production |
| Topics | Serotonin |
| Key points | Serotonin and hallucinogens increase cGMP production in rat frontal cortical slices. DOM's effect is mediated by 5-HT2A receptors, and DPAT's effect by 5-HT1A receptors, indicating these receptor subtypes activate cGMP signaling. |
Abstract
Elucidating the mechanisms of action of hallucinogens has become an increasingly important area of research as their abuse has grown in recent years. Although serotonin receptors appear to play a role in the behavioral effects of the phenethylamine and indoleamine hallucinogens, the signaling pathways activated by these agents are unclear. Here it is shown that administration of serotonin (5-hydroxytryptamine, 5-HT) increased cyclic guanosine monophosphate (cGMP) production in frontal cortical slices of rat brain. The effect of 5-HT was greater than that of N-methyl-D-aspartate (NMDA), a stimulant of cGMP formation in the central nervous system. The 5-HT(2A/2C) receptor phenethylamine agonist, 2,5-dimethoxy-4-methylamphetamine (DOM), increased cGMP content in the slices. Additionally 8-hydroxy-2-(di-n-propylamino)tetralin (DPAT), a 5-(HT1A/7) receptor agonist also increased cGMP production. Stimulation of cGMP formation by DOM was prevented by a 5-HT(2A/2C) receptor antagonist, pirenperone, as well as by a 5-HT2A receptor selective antagonist, MDL100907. A 5-HT2C receptor antagonist, SB242084, did not block the effect of DOM. Stimulation of cGMP production by DPAT was blocked by the 5-HT1A receptor antagonist, WAY100635. Stimulation of cGMP formation by serotonin could be prevented by pirenperone or WAY100635. In summary, activation of serotonin 5-HT1A and 5-HT2A receptors increase brain cGMP levels.
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 |
Citations in the library
Cites 10
- Psilocybin induces schizophrenia-like psychosis in humans via a serotonin-2 agonist action Neuroreport December 1, 1998
- Evidence for 5-HT2 involvement in the mechanism of action of hallucinogenic agents. Life Sciences December 17, 1984
- Control of Serotonergic Function in Medial Prefrontal Cortex by Serotonin-2A Receptors through a Glutamate-Dependent Mechanism Journal of Neuroscience December 15, 2001
- Lysergic acid diethylamide and 2,5-dimethoxy-4-methylamphetamine are partial agonists at serotonin receptors linked to phosphoinositide hydrolysis. Journal of Pharmacology and Experimental Therapeutics September 1, 1988
- The paradox of 5-methoxy-N,N-dimethyltryptamine: an indoleamine hallucinogen that induces stimulus control via 5-HT1A receptors. Pharmacology, Biochemistry, and Behavior 2000
and 5 more in the library