Diurnal variation in 5-HT1B autoreceptor function in the anterior hypothalamus in vivo: effect of chronic antidepressant drug treatment - PubMed (original) (raw)

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

T J Sayer et al. Br J Pharmacol. 1999 Apr.

Abstract

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 microM 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 microM) was prevented by concurrent infusion of methiothepin (1 and 10 microM) into the anterior hypothalamus via the microdialysis probe. Infusion of methiothepin alone (1.0 and 10 microM) increased (15 and 142% respectively) 5-HT output. 3. Infusion of RU24969 (5 microM) 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.

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Figures

Figure 1

Figure 1

Effect of removing calcium ions from the perfusing medium on the level of 5-HT in dialysate collected from the anterior hypothalamus. Concentric microdialysis probes were perfused with aCSF containing (in m

M

): NaCl 147, KCl 4, CaCl2 4 and citalopram 1 μ

M

and samples collected every 15 min. **P<0.01 vs pooled control (two way ANOVA). Data are expressed as a percentage of the concentration of 5-HT in the two dialysate samples taken immediately prior to any intervention (control value). Each point represents the mean value with s.e.mean shown by vertical bars. Control _n_=12, calcium free buffer _n_=4.

Figure 2

Figure 2

Effects of infusion of (a) the 5-HT1A agonist 8-OH-DPAT and (b) the 5-HT1A/1B agonist RU24969 on 5-HT output in the anterior hypothalamus. (a) 8-OH-DPAT, 1 μ

M

(_n_=4) was infused for 15 min through the probe; pooled control, _n_=12. (b) RU24969, 0.1 μ

M

_n_=4, 1 μ

M

_n_=4, 10 μ

M

_n_=6) was infused for 15 min; pooled control, _n_=12. *P<0.05, **P<0.01 vs pooled control value (two-way ANOVA). Data are expressed as a percentage of the concentration of 5-HT in the two dialysate samples taken immediately prior to any intervention (control value), each point represents mean with the s.e.mean indicated by vertical bars.

Figure 3

Figure 3

Effects of methiothepin infusion on the effects of RU24969 on 5-HT output in the anterior hypothalamus. Methiothepin was infused for 15 min and then either co-infused with RU24969 for a further 15 min (lined bar) or infused alone (solid bar) (a) 1 μ

M

methiothepin+1 μ

M

RU24969 (_n_=4) and 1 μ

M

methiothepin (_n_=4), pooled control, _n_=12. *P<0.05 vs pooled control value, #P<0.05, ##P<0.01 vs 1 μ

M

RU24969 (two-way ANOVA). (b) 10 μ

M

methiothepin+5 μ

M

RU24969 (_n_=4) and 10 μ

M

methiothepin (_n_=5), pooled control, _n_=12. **P<0.01 vs pooled control value, ##P<0.01 vs 5 μ

M

RU24969 (two-way ANOVA). Data are expressed as a percentage of the concentration of 5-HT in the two dialysate samples taken immediately prior to any intervention (control value), as mean with s.e.mean indicated by vertical bars.

Figure 4

Figure 4

Effects of a 15 min infusion of 5 μ

M

RU24969 at (a) mid-light and (b) end-light on 5-HT output in the anterior hypothalamus. (a) control (_n_=6) and 5 μ

M

RU24969 (_n_=4). **P<0.01 vs control value for mid-light (two-way ANOVA). (b) control (_n_=5) and 5 μ

M

RU24969 (_n_=4). **P<0.01 vs control value for end-light (two-way ANOVA). Data are expressed as a percentage of the concentration of 5-HT in the two dialysate samples taken immediately prior to any intervention (control value), as mean with the s.e.mean indicated by vertical bars.

Figure 5

Figure 5

Rats were treated chronically with paroxetine hydrochloride (10 mg kg−1 i.p.), desipramine hydrochloride (10 mg kg−1 i.p.) or saline and the effect of a 15 min infusion of 5 μ

M

RU24969 re-assessed at (a) mid-light and (b) end-light. (a) saline-treated+5 μ

M

RU24969 (_n_=4), paroxetine-treated+5 μ

M

RU24969 (_n_=4) and desipramine-treated+5 μ

M

RU24969 (_n_=5). *P<0.05, vs saline-treated rats (two-way ANOVA). (b) saline-treated+5 μ

M

RU24969 (_n_=6), paroxetine-treated+5 μ

M

RU24969 (_n_=4) and desipramine-treated+5 μ

M

RU24969 (_n_=4). *P<0.05, **P<0.01 vs saline-treated animals (two-way ANOVA). Data are expressed as a percentage of the concentration of 5-HT in the two dialysate samples taken immediately prior to any intervention (control value), as mean with s.e.mean indicated by vertical bars.

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