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- W1982419021 abstract "There are several demonstrations of constitutive receptor activity whereby receptor signaling occurs in the absence of ligand binding. Under such conditions, drugs can increase (agonist), decrease (inverse agonist), or have no effect (neutral antagonist) on receptor signaling. To test whether drug discrimination can be used to study these three different drug actions, separate groups of rats (n=8/group) were trained to discriminate between saline and either an agonist (1-(2,5-dimethoxy-4-methylphenyl)-2-aminopropane [DOM], 0.56 mg/kg), an inverse agonist (MDL100907, 0.1 mg/kg), or a neutral antagonist (ketanserin, 1.0 mg/kg) at serotonin (5-HT)2A receptors, the primary site of action for many hallucinogens. Stimulus control was adequate for testing in all three groups after an average of 33-35 training sessions. The discriminative stimulus effects of DOM were attenuated by MDL100907 and by ketanserin and the discriminative stimulus effects of MDL100907 and ketanserin were attenuated by DOM. Neither MDL100907 nor ketanserin occasioned DOM-lever responding and DOM did not occasion MDL100907- or ketanserin-lever responding. Ketanserin occasioned >90% MDL100907-lever responding whereas MDL100907 occasioned only 50% ketanserin-lever responding. However, the combination of MDL100907 and the alpha2 adrenergic receptor antagonist prazosin occasioned >90% ketanserin-lever responding, suggesting that the ketanserin discriminative stimulus comprises 5-HT and alpha2 adrenergic components. That a ketanserin discrimination was established indicates that it is not acting as a neutral antagonist at 5-HT2A receptors, that constitutive activity is not significant under these conditions, or that it has effects by antagonism of endogenous 5-HT. Depletion of 5-HT in these rats failed to provide convincing evidence for constitutive activity at 5-HT2A receptors. CPF is supported by a Senior Scientist Award (DA17918)." @default.
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- W1982419021 date "2008-06-01" @default.
- W1982419021 modified "2023-09-27" @default.
- W1982419021 title "IS THERE BEHAVIORAL EVIDENCE FOR CONSTITUTIVE ACTIVITY AT 5-HT2ARECEPTORS?" @default.
- W1982419021 doi "https://doi.org/10.1111/j.1530-0277.2008.00689_2.x" @default.
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