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)

Serotonin (5-HT) and cholecystokinin (CCK) are involved in the development of anxiety. There are only few data suggesting interactions between CCK and 5-HT under aversive conditions. In our study the cholecystokinin tetrapeptide (CCK-4) (10 microg/kg) induced 'anxious' behaviour and potentiated the increase of 5-HT release on the elevated plus maze (X-maze). The 'anxiolytic' 5-HT1A agonist 8-hydroxy-2-(di-n-propyl amino) tetralin (8-OH-DPAT; 0.3 mg/kg) reduced basal 5-HT and the increase in 5-HT release on the X-maze. 8-OH-DPAT given simultaneously with CCK-4, blocked the effects of CCK-4. The results demonstrate an interaction between CCK and 5-HT1A mechanisms via the influence on cortical 5-HT release.
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PMID:Cortical 5-HT-CCK interactions and anxiety-related behaviour of guinea-pigs: a microdialysis study. 920 3

1. The ability of 5-HT2 and 5-HT4 receptor antagonists to modify the disinhibitory profile of diazepam and other agents was investigated in male BKW mice in the light/dark test box. 2. The 5-HT2A/2B/2C receptor antagonists ritanserin, MDL11939 and RP62203 and also methysergide, which failed to modify mouse behaviour when administered alone, caused dose-related enhancements (4 to 8 fold) in the potency of diazepam to disinhibit behavioural responding to the aversive situation of the test box. 3. Ritanserin was shown to enhance the disinhibitory potency of other benzodiazepines, chlordiazepoxide (4 fold), temazepam (10 fold) and lorazepam (10 fold), the 5-HT1A receptor ligands, 8-OH-DPAT (25 fold), buspirone (100 fold) and lesopitron (500 fold), the 5-HT3 receptor antagonists, ondansetron (100 fold) R(+)-zacopride (100 fold) and S(-)-zacopride (greater than a 1000 fold), the substituted benzamides, sulpiride (10 fold) and tiapride (5 to 10 fold) and the cholecystokinin (CCK)A receptor antagonist, devazepide (100 fold). It also reduced the onset of action of disinhibition following treatment with the 5-HT synthesis inhibitor parachlorophenylalanine. Ritanserin failed to enhance the disinhibitory effects of the CCKB receptor antagonist CI-988, the angiotensin AT1 receptor antagonist losarten or the angiotensin converting enzyme inhibitor ceranapril. 4. The 5-HT4 receptor antagonists SDZ205-557, GR113808 and SB204070 caused dose-related reductions in the disinhibitory effect of diazepam, returning values to those shown in vehicle treated controls. The antagonists failed to modify mouse behaviour when administered alone. 5. GR113808 was also shown to cause a dose-related antagonism of the disinhibitory effects of chlordiazepoxide, lorazepam, 8-OH-DPAT, buspirone, lesopitron, ondansetron, R(+)-zacopride, sulpiride, tiapride, devazepide, CI-988, losarten, ceranapril and parachlorophenylalanine. 6. It was concluded that in BKW mice (a) the failure of 5-HT2 and 5-HT4 receptor antagonists when administered alone to modify behaviour in the light/dark test indicates an absence of an endogenous 5-HT tone at the 5-HT2 and 5-HT4 receptors and (b) the enhancement by the 5-HT2 receptor antagonists and attenuation by the 5-HT4 receptor antagonists of drug-induced disinhibition indicates a plurality of 5-HT receptor involvement in the mediation of drug-induced disinhibitory profiles in the mouse.
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PMID:The influence of 5-HT2 and 5-HT4 receptor antagonists to modify drug induced disinhibitory effects in the mouse light/dark test. 940 75

The influence of cholecystokinin (CCK-8S) and serotonin (5-HT) on the discharge rate of spontaneously active ventromedial hypothalamic (VMH) neurons was investigated in brain slices. Drugs were drop-applied individually and concomitantly into the slice chamber. CCK-8S (0.1-2.5 microM) produced a dose-dependent increase in firing rate mainly mediated by the CCK(B) receptor subtype, because Suc-CCK-4 (a CCK(B) receptor agonist) acted like CCK-8S and A-71378 (a CCK(A) receptor agonist) rarely induced excitatory effects. The main response to serotonin application (2-20 microM) was an inhibition that could be mimicked by 8-OH-DPAT (a 5-HT1A receptor agonist). S-UH-301 (a 5-HT1A receptor antagonist) reversibly diminished or blocked this effect. Other 5-HT agonists like DOI and 2-Methyl-5-HT did not evoke relevant responses. Co-administration of CCK-8S and 5-HT induced counteracting effects at which CCK-8S significantly reduced the prevailing suppressive effect of serotonin. It is concluded that both substances, CCK and 5-HT, have a reciprocal influence on the regulation of neuronal activity within the VMH, a structure, which is involved in the mediation of signals for the state of satiety.
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PMID:Interactive effects of cholecystokinin-8S and serotonin on spontaneously active neurons in ventromedial hypothalamic slices. 984 2

The effect of chronic fluoxetine and ipsapirone treatment on the anxiogenic effect of centrally administered cholecystokinin (CCK) was studied in the social interaction test in male Sprague-Dawley rats. Intracerebroventricular injection of unsulfated CCK-8 significantly decreased total interaction time and locomotor activity and caused some increase in selfgrooming and a reduction in rearing behaviour in a familiar arena in low light conditions. The selective serotonin reuptake inhibitor antidepressant fluoxetine alone (5 mg/kg, i.p.) also had clear acute anxiogenic actions (decrease in total interaction time, locomotor activity, rearing, increase in selfgrooming) after single dosing, but all these effects were omitted after chronic (3 weeks) treatment. In contrast, a single injection of the 5-HT1A receptor partial agonist ipsapirone (5 mg/kg, i.p.) alone had only motor effects (decrease in selfgrooming and rearing), and these effects were preserved after chronic treatment. Chronic fluoxetine treatment (5 mg/kg per day, 3 weeks) abolished the effects of CCK-8 (1 nmol/rat, i.c.v.). Chronic treatment with ipsapirone (5 mg/kg per day, 3 weeks) partially attenuated the effects of CCK-8 (1 nmol/rat, i.c.v.). Our studies provide further evidence for a 5-HT/CCK interaction in the regulation of anxiety.
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PMID:Anxiogenic effect of central CCK administration is attenuated by chronic fluoxetine or ipsapirone treatment. 1021 69

In line with the idea that cholecystokinin (CCK) is involved in anxiety-related behaviours, previous investigations showed that stressful conditions and an 'anxiogenic' drug, yohimbine, increased the cortical release of CCK like-material (CCKLM) in awake rats, and that this effect could be prevented by diazepam. Here, we investigated whether other anxiolytic drugs such as 5-HT1A receptor agonists could also affect cortical CCKLM release. Indeed, neither buspirone (1 mg/kg i.p.), alnespirone (1 mg/kg i.p.) nor lesopitron (3 mg/kg i.p.) affected, on their own, CCKLM release. However, pretreatment with the latter drugs completely abolished the stimulatory effect of restraint stress on the peptide outflow. As expected of the involvement of 5-HT1A receptors, tertatolol (10 mg/kg i.p) markedly reduced the inhibitory effect of buspirone on restraint stress-evoked CCKLM overflow. On the other hand, pretreatment with buspirone, alnespirone or lesopitron also inhibited the stimulatory effect of yohimbine (5 mg/kg i.p.) on cortical CCKLM outflow. These data support the idea that the anxiolytic action of 5-HT1A receptor agonists could be mediated, at least partly, through their inhibitory influence on cortical CCK-ergic systems.
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PMID:Prevention by 5-HT1A receptor agonists of restraint stress- and yohimbine-induced release of cholecystokinin in the frontal cortex of the freely moving rat. 1022 56

The present study describes the role of 5-HT1A receptors in the serotonergic control of food intake in obese Zucker rats of different ages. In addition, serotonin (5-HT) and cholecystokinin (CCK) content and 5-HT turnover were determined in various brain regions. The 5-HT1A receptor agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT; 100 microg/kg) stimulated food intake in 3-month-old lean control rats but inhibited feeding in obese Zucker rats (300 microg/kg). This pattern remained the same in 6-month-old rats. At 10 months of age, 8-OH-DPAT lost its inhibitory activity in the obese rats but still stimulated feeding in lean controls (300 microg/kg). 5-HT levels were higher in the hypothalamus and in the frontal and parietal cortices of 3-month-old obese Zucker rats and were associated with a lower cortical turnover. In the parietal cortex and the hypothalamus of 6-month-old rats, 5-HT levels were still higher, linked with a lower hypothalamic turnover. No differences were observed in 10-month-old rats. CCK content was not different between obese Zucker rats and lean rats. The persistently different feeding responses to 8-OH-DPAT in obese Zucker rats and lean controls may be related to changes in brain 5-HT metabolism in the obese Zucker rats.
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PMID:Role of 5-HT1A receptors in the control of food intake in obese Zucker rats of different ages. 1190 Aug 12

Aversive experiences in early life are thought to dispose to psychopathologies such as mood or anxiety disorders. In a two-hit stress model, we assessed the effects of juvenile and/or adult stress on the 5-HT-mediated modulation of synaptic inhibition of ventral dentate gyrus granule cells. Combined but not single stress exposure led to a significant reduction in activity and increased anxiety-like behavior. Similarly, the 5-HT1A receptor-mediated inhibition of evoked inhibitory postsynaptic currents (IPSCs) of granule cells was only reduced in single stress exposed animals. This was also true for the number of granule cells responding with a 5-HT3 receptor-dependent burst of miniature IPSCs. 5-HT3 receptors are expressed on cholecystokinin (CCK)+ basket cells in the hippocampus. In fact, we observed a reduction of steady-state mRNA levels of CCK+ basket cell markers after single juvenile or adult stress and partial recovery after combined stress, thus matching the electrophysiological findings. Adaptive changes in 5-HT-mediated modulation of synaptic inhibition and CCK+ basket cells in the DG may help to maintain normal levels of anxiety after single juvenile or adult stress exposure, as indicated by the increased anxiety that accompanies the loss of this regulation upon combined stress.
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PMID:5-HT receptor-mediated modulation of granule cell inhibition after juvenile stress recovers after a second exposure to adult stress. 2574 30


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