Regulation of the release of serotonin in the dorsal raphe nucleus by alpha1 and alpha2 adrenoceptors

To investigate the modulation of serotonin release in the dorsal raphe nucleus (DRN) by alpha(1) and alpha(2) adrenoceptors, dual-probe microdialysis was performed in conscious rats. The specific alpha(1) and alpha(2) adrenoceptor agonists and antagonists were locally infused into the DRN via retrograde microdialysis. The release of serotonin was simultaneously sampled from the DRN and prefrontal cortex (PFC). Infusion of the alpha(1) adrenoceptor agonist cirazoline into the DRN (100 microM) produced an increase in the release of serotonin in the DRN to 200% of the basal levels, but no effect was seen in the PFC. After infusion of the alpha(1) adrenoceptor antagonist prazosin into the DRN (100 microM) the release of serotonin decreased in the DRN and PFC to about 40% and 65% of the basal levels, respectively. Infusion of the alpha(2) adrenoceptor agonist clonidine into the DRN (100 microM) slightly but significantly decreased the level of serotonin in the DRN as well as in the PFC to about 70% of the basal levels. Infusion of the alpha(2A) adrenoceptor antagonist BRL 44408 into the DRN (100 microM) caused an increase of serotonin release in the DRN to 270% of the basal levels, but at the same time no changes were seen in the extracellular levels of serotonin in the PFC. The present study demonstrates that alpha(1) as well as alpha(2) adrenoceptors in the DRN modulate the release of serotonin in the DRN, and that alpha(1) adrenoceptors in the DRN are maximally stimulated during resting conditions.