Title: Single-dose 8-OH-DPAT pretreatment does not Induce tachyphylaxis to the 5-HT release-reducing effect of 5-HT1A autoreceptor agonists
Abstract: It has recently been suggested (hat central 5-HT1A autoreceptors are already desensitised after single-dose 5-HT1A agonist treatment. In turn, this would lead to an attenuated feedback suppression of transmitter release from 5-HT neurones, and thus to enhanced 5-HT synaptic transmission. In the present study in vivo brain microdialysis techniques were used in an attempt to test this hypothesis. The results show that single-dose pretreatment with the reference 5-HT1A receptor agonisl 8-hydroxy-2-(din-propylamino) tetralin, 8-OH-DPAT. (i) did not significantly alter the baseline output of 5-HT in the rat ventral hippocampus 24 h later, and (ii) did not alter the release-reducing response to 5-HT1A agonist (8-OH-DPAT. ipsapirone or BMY 7378) challenge under the same conditions. These observations indicate thai the functional rcsponsiveness of the 5-HT release-controlling s-ht)a autoreceptors is maintained after bolus 8-OH-DPAT pretreatment. When related to the acute 8-OH-DPAT-induced reaction in raphe 5-HT1A radioligand binding density recently reported by others, the present results arc consistent with a large ional overcapacity of this 5-HT1A receptor population. The mechanism by which 5-HT1A receptor-mediated hypothermia and hyperphagia are rapidly attenuated by a previous large single dose of a 5-HT1A receptor agonist remains to be explained.
Publication Year: 1991
Publication Date: 1991-06-01
Language: en
Type: article
Indexed In: ['crossref', 'pubmed']
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Cited By Count: 13
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