Diurnal variation in 5‐HT 1B autoreceptor function in the anterior hypothalamus in vivo : effect of chronic antidepressant drug treatment

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. Infusion of the 5‐HT 1A/1B agonist 5‐methoxy‐3‐(1,2,3,6‐tetrahydro‐4‐pyridyl)‐1H‐indole (RU24969) 0.1, 1.0 and 10 μ 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 μ M ) was prevented by concurrent infusion of methiothepin (1 and 10 μ M ) into the anterior hypothalamus via the microdialysis probe. Infusion of methiothepin alone (1.0 and 10 μ M ) increased (15 and 142% respectively) 5‐HT output. Infusion of RU24969 (5 μ 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. 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‐HT 1B autoreceptor was more markedly attenuated at end‐light. The data show that, as defined by the response to RU24969, the function of the 5‐HT 1B 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.British Journal of Pharmacology (1999) 126 , 1777–1784; doi: 10.1038/sj.bjp.0702535