Diurnal variation in 5-HT1B autoreceptor function in the anterior hypothalamus in vivo:: effect of chronic antidepressant drug treatment

1 Intracerebral microdialysis was used to examine the function of the terminal 5-hydroxytryptamine (5-HT) autoreceptor in the anterior hypothalamus of anaesthetized rats at two points in the light phase of the light-dark cycle. 2 Infusion of the 5-HT1A/1B agonist 5-methoxy-3-(1,2,3,6-tetrahydro-4-pyridyl)-1H-indole (RU24969) 0.1, 1.0 and 10 mu M through the microdialysis probe led to a concentration-dependent decrease (49, 56 and 65% respectively) in 5-HT output. The effect of RU24969 (1 and 5 mu M) was prevented by concurrent infusion of methiothepin (1 and 10 mu M) into the anterior hypothalamus via the microdialysis probe. 3 Infusion of methiothepin alone (1.0 and 10 mu M) increased (15 and 142% respectively) 5-HT output. 3 Infusion of RU24969 (5 mu M) through the probe at mid-light and end-light resulted in a quantitatively greater decrease in 5-HT output at end-light compared with mid-light. 4 Following treatment with either paroxetine hydrochloride (10 mg kg(-1) i.p.) or desipramine hydrochloride (10 mg kg(-1) i.p.) for 21 days the function of the terminal 5-HT1B autoreceptor was more markedly attenuated at end-light. 5 The data show that, as defined by the response to RU24969, the function of the 5-HT1B receptors that control 5-HT output in the anterior hypothalamus is attenuated following chronic desipramine or paroxetine treatment in a time-of-day-dependent manner.