Pharmacological characteristics of 5‐hydroxytryptamine autoreceptors in rat brain slices incorporating the dorsal raphe or the suprachiasmatic nucleus

Open Access
Publisher Website
Google Scholar
Abstract
1 Changes in extracellular concentrations of 5-hydroxytryptamine elicited by electrical stimulation in rat brain slices containing the dorsal raphe nucleus and the suprachiasmatic nucleus were monitored with fast cyclic voltammetry. 2 Using pseudo single pulse stimulation (5 pulses applied at 100 Hz) we have shown that the release of 5-hydroxytryptamine in the dorsal raphe and the suprachiasmatic nucleus can be regulated by autoreceptors in both brain regions. 3 In the suprachiasmatic nucleus, 5-carboxamidotryptamine, RU24969, 1-(m-trifluoromethylphenyl) piperazine and sumatriptan caused a concentration-dependent inhibition of stimulated 5-hydroxytryptamine overflow in the range 1 × 10−9 m to 3 × 10−6 m. The actions of 5-carboxamidotryptamine and RU24969 were reversed competitively by methiothepin (10−8 m to 10−6 m); Schild plots revealed pKB values of 7.9 and 8.1. By contrast, ipsaparone and 8-hydroxy-2(di-n-propylamino)tetralin (8-OH-DPAT) are not effective 5-hydroxytryptamine autoreceptor agonists in the suprachiasmatic nucleus. 4 Isamoltane (10−6 m), the putative 5-HT1B receptor antagonist, blocked the responses to RU24969 (10−6 m) and 1-(m-trifluoromethylphenyl)piperazine (10−6 m) in the suprachiasmatic nucleus. 5 In the dorsal raphe nucleus, 8-OH-DPAT, ipsapirone, RU24969, 5-carboxamidotryptamine, and sumatriptan (all 1×10−8 m to 3×10−6 m) produced a concentration-dependent reduction in the stimulated release of 5-hydroxytryptamine. The maximum effect observed was less than that seen in the suprachiasmatic nucleus. 6 Methiothepin (1 × 10−7 m) blocked the effect of 5-carboxyamidotryptamine (10−8 m to 10−6 m) in the dorsal raphe nucleus while propranolol (10−6 m) and NAN-190 (10−6 m) but not isamoltane (10−6 m) were found to block significantly the effect of ipsapirone (10−6 m). 7 We conclude, that drugs with 5-HT1A binding activity act as agonists in the dorsal raphe nucleus while drugs showing some activity for 5-HT1B and 5-HT1D binding sites, act as agonists in the suprachiasmatic nucleus. Our results confirm predictions from binding studies, that functional 5-HT autoreceptors regulating release of endogenous 5-HT have different drug specificity in the dorsal raphe and suprachiasmatic nucleus.