Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P08908 (5-HT1A)
 5,574 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Drugs that enhance serotonergic neurotransmission reduce food intake by directly or indirectly activating serotonergic receptors. In contrast drugs that inhibit serotonergic neurotransmission such as the 5-HT1A agonist 8-hydroxy-2-(di-n-propyl-amino)tetralin (8-OH-DPAT) stimulate food intake. The present study examined the effects of 8-OH-DPAT on the feeding suppressant action of the indirect 5-HT agonists fenfluramine (FEN; 0.63-2.5 mg/kg) and fluoxetine (FLU; 2.5-10 mg/kg), as well as the 5-HT1B/2C agonist 1-(3-trifluoromethylphenyl)piperazine (TFMPP; 0.5-2 mg/kg). 8-OH-DPAT (62.5-250 microg/kg) was administered 5 min prior to FEN, FLU or TFMPP, injected 30 min before food access. While FEN, FLU and TFMPP dose-dependently reduced 2 h food intake, 8-OH-DPAT stimulated eating behavior. 8-OH-DPAT (62.5-250 microg/kg) pretreatment reversed the anorectic action of FEN (1.25 mg/kg) and FLU (5 mg/kg) but not TFMPP (1 mg/kg). Separate groups of rats were injected with 5,7-dihydroxytryptamine (5,7-DHT; 3 microg free base) into both the dorsal and median raphe, which resulted in extensive 5-HT depletion in hypothalamus (80%), striatum and hippocampus (90%). In both 5, 7-DHT and vehicle-injected rats, FEN (1.25 mg/kg) and FLU (5 mg/kg) suppressed feeding. In 5,7-DHT treated rats, however, the ability of 8-OH-DPAT (125 microg/kg) to block FEN and FLU induced anorexia was attenuated. That is, 8-OH-DPAT pretreatment did not reverse the feeding inhibitory effects of either FEN or FLU. Further, the ability of FEN and FLU to suppress food intake was not altered by the 5,7-DHT lesion. These findings suggest that the reversal of FEN and FLU anorexia by 8-OH-DPAT is partially dependent on the integrity of brain 5-HT systems since their disruption compromises the ability of this 5-HT1A agonist to antagonize the feeding suppressant action of either FEN or FLU. However, the ability of treatments which impair 5-HT neurotransmission to reverse FEN and FLU induced suppression of food intake may depend upon whether this impairment is acute and reversible (8-OH-DPAT), or chronic and irreversible (5,7-DHT).
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PMID:Reversal of fenfluramine and fluoxetine anorexia by 8-OH-DPAT is attenuated following raphe injection of 5,7-dihydroxytryptamine. 968 86

Anxiolytics that act as GABAA agonists and those that act as 5-HT1A receptor agonists all reduce the frequency of hippocampal rhythmic slow activity (RSA). Changes in RSA have been linked to changes in behavioural inhibition and therefore anxiety - but this has not been tested with specific serotonin reuptake inhibitors, which are antidepressant and anxiolytic; therefore we tested the effects of fluoxetine on RSA and behavioural inhibition. Fluoxetine (FLU; 10 and 20 mg/kg, intraperitoneally) produced a dose-related reduction in the frequency of reticular-elicited RSA. Groups of rats received, intraperitoneally, either (i) saline, or 5 mg/kg fluoxetine, or 10 mg/kg fluoxetine; or (ii) saline, or 20 mg/kg fluoxetine, or 6.6 mg/kg of the 5-HT1A agonist buspirone (BUS) and were tested on a fixed interval 60-s schedule and a differential reinforcement of low rates 15-s schedule. FLU at 5 mg/kg produced effects similar to low doses of BUS and other anxiolytics. FLU (10 and 20 mg/kg) produced effects more like those reported earlier for higher doses of BUS. These results continue to link anxiolysis, RSA and behavioural inhibition, and suggest that serotonergic anxiolytics share some of the central actions of GABAergic anxiolytics, but at higher doses, administered acutely, have distinct side effects that can obscure their anxiolytic action in behavioural tasks.
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PMID:Effects of fluoxetine on hippocampal rhythmic slow activity and behavioural inhibition. 1846 43