Firing of 5-HT neurones in the dorsal and median raphe nucleus in vitro shows differential α 1-adrenoceptor and 5-HT 1A receptor modulation

Abstract

The median raphe nucleus and dorsal raphe nucleus together are the major source of ascending 5-HT projections. Here, using in vitro extracellular single unit electrophysiology we examined the responses of individual neurones in the rat median raphe nucleus and dorsal raphe nucleus to α 1-adrenoceptor and 5-HT 1A receptor activation and made comparisons between the two nuclei. In the presence of the α 1-adrenoceptor agonist phenylephrine (1 μM) all spontaneously active neurones recorded in the median and dorsal raphe nuclei fired slowly (<5 Hz) and regularly. Most were inhibited by 5-HT (10–50 μM), although a few were excited by 5-HT. 5-HT-induced inhibition was attenuated by the 5-HT 1A receptor antagonist, WAY100635 (100 nM). Compared to those in the dorsal raphe nucleus, the neurones in the median raphe nucleus which were inhibited by 5-HT had: (1) lower basal firing rates in the continuous presence of phenylephrine (1 μM), (2) smaller excitatory responses to higher concentrations of phenylephrine (3–10 μM), (3) smaller excitatory responses to brief application of norepinephrine (10–100 μM) and (4) smaller inhibitory responses to 5-HT (10–50 μM). The lower sensitivity of median raphe neurones to α 1-adrenoceptor excitation and 5-HT 1A receptor inhibition will have consequences for 5-HT neurotransmission in forebrain regions innervated by the two nuclei.