This study reviews the role of the serotonin 5-HT2A receptor in learning as measured by the acquisition of the rabbit's classically conditioning nictitating membrane response, a component of the eyeblink response. Agonists at the 5-HT2A receptor including LSD (d-lysergic acid diethylamide) enhanced associative learning at doses that produce cognitive effects in humans. Some antagonists such as...
The effect of prior exposure to methylenedioxyamphetamine (MDA) on behavioural and neurochemical responses to fluoxetine were assessed in a rat model of antidepressant action. MDA (7.5 mg/kg, i.p.) was administered to rats twice daily for 4 consecutive days, and 4 weeks later the behavioural effect of fluoxetine (5 or 20 mg/kg; i.p. x 3) was examined in the modified rat forced-swimming test. In...
In studies of the SAR of phenethylamine-type serotonin 5-HT(2A) receptor agonists, substituted conformationally constrained tetrahydronaphthofurans were designed to investigate the optimal conformation of the 2-aminoethyl moiety. These compounds were tested using in vitro assays for affinity at 5-HT(1A), 5-HT(2A), and 5-HT(2C) receptors. The benzofuran-containing analogues, 6a and 6b, had...
Plasma levels of parent compounds and metabolites were determined in adult rhesus monkeys after doses of either 5mg/kg d-fenfluramine (FEN) or 10mg/kg d-3, 4-methylenedioxymethamphetamine (MDMA) i.m. twice daily for four consecutive days. These treatment regimens have been previously shown to produce long-term serotonin (5-HT) depletions. Peak plasma levels of 2.0+/-0.4 microM FEN were reached...
The effect of 5-HT(2) receptor activation on brain glycogen and the extracellular concentration of glucose was investigated in the present study. An injection of 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) (2 mg/kg, i.p.) or mescaline (10 mg/kg, i.p.) at an ambient temperature of 29 degrees C produced a 35-45% decrease in brain glycogen that persisted for at least 2 h. DOI also...
Potent serotonin (5-HT) reuptake inhibitors are the only drugs that consistently exert a therapeutic action in obsessive-compulsive disorder (OCD). Given that some hallucinogens were reported to exert an anti-OCD effect outlasting their psychotomimetic action, possible modifications of neuronal responsiveness to 5-HT by LSD were examined in two rat brain structures: one associated with OCD, the...
Incorporation coefficients k* of intravenously injected [3H]arachidonic acid from blood into brain reflect the release from phospholipids of arachidonic acid by receptor-initiated activation of phospholipase A2 (PLA2). In unanesthetized adult rats, 2.5 mg/kg intraperitoneally (i.p.) (±)2,5-dimethoxy-4-iodophenyl-2-aminopropane (DOI), which is a 5-HT2A/2C receptor agonist, has been reported to...
Previously the NMDA (N-methyl-D-aspartate) receptor (NMDAR) antagonist ketamine was shown to disrupt generation of the auditory event-related potential (ERP) mismatch negativity (MMN) and the performance of an 'AX'-type continuous performance test (AX-CPT)--measures of auditory and visual context-dependent information processing--in a similar manner as observed in schizophrenia. This...
Based on experiment and computational simulation, we present a structural explanation for the differing efficacies of indole agonists at the human serotonin 5-HT2A receptor (5HT2AR). We find that serotonin [5-hydroxytryptamine (5-HT)] forms hydrogen-bonds with Ser3.36 in helix 3 and Ser5.46 in helix 5. Disruption of these hydrogen bonds by methyl-substitution of the cationic primary amine or of...
Abstract Recent [ 123 I]β‐CIT single‐photon emission computed tomography (SPECT) studies revealed decreased serotonin transporters (SERT) density in the brain of humans with a history of MDMA (“Ecstasy”) use. However, [ 123 I]β‐CIT SPECT has until now not been validated as a method for detecting such serotonergic lesions. Therefore, the present study was undertaken. Following baseline [ 123...