Reserpine suppression of dorsal raphe neuronal firing: mediation by adrenergic system

Reserpine, which induces a depletion of both serotonin (5-HT) and norepinephrine (NE) in brain, suppresses the firing of 5-HT cells in the dorsal raphe. Since these cells are known to be inhibited by either increased 5-HT "availability" or a reduction of adrenergic tone, studies were aimed at defining the role of these transmitter systems in mediating reserpine's suppression of 5-HT cell firing. Intraventricular injections of 6-hydroxydopamine, which destroyed NE terminals in the raphe region, prevented reserpine's effect on 5-HT cell activity. Both 1-amphetamine, which releases endogenous NE, and high doses of clonidine (200-400 μg/kg), a post-synaptic α-agonist, reversed the reserpine-induced depression of firing. Pretreatment with parachlorophenylalanine, which inhibits 5-HT synthesis, did not block either reserpine's depressant effect or amphetamine's ability to restore activity. Taken together, these results suggests that reserpine suppresses 5-HT cell firing by interfering with tonic adrenergic transmission, a normally present pre-requisite for 5-HT cell firing. Local iontophoresis of small amounts of NE dramatically reversed reserpine's depressant effect, but not that produced by systemically administered LSD. Since the dorsal raphe receives an adrenergic innervation, catecholamine terminals there could be responsible for providing the adrenergic tone upon which the firing of 5-HT cells depends. he possible involvement of local GABAergic interneurons in mediating an indirect NE disinhibition of 5-HT cell activity is discussed.