Activation of 5-HT1A receptors potentiates the clonidine inhibitory effect in the locus coeruleus

Using in vivo extracellular recordings, we have examined the effect of the application of the prototypical 5-HT1A receptor agonist 8-hydroxy-2-(di-n-propylamino)-tetralin (8-OH-DPAT), on the firing rate of locus coeruleus neurons. 8-OH-DPAT (1 microgram/kg, i.v.) did not modify the basal activity of the locus coeruleus but shifted to the left the dose-response curve for the clonidine induced inhibition of firing rate and reduced the corresponding ED50 by 77%. 2-[2-[4-(o-methoxyphenyl)piperazin-1-yl]ethyl]-4,4-dimethyl-1,3(2H ,4H)-isoquinolinedione (ARC 239; 75 micrograms/kg, i.v.), and chlorpromazine (75 micrograms/kg, i.v.) also shifted to the left the dose-response curve for clonidine and reduced by 38 and 46%, respectively, the ED50, while slightly increasing the basal firing rate. The results indicated that 5-HT1A receptors may modulate the responses mediated by alpha 2A-adrenoceptors in the locus coeruleus.