SELECTIVE BLOCKADE OF SEROTONIN(2C 2B) RECEPTORS ENHANCES DOPAMINE RELEASE IN THE RAT NUCLEUS-ACCUMBENS/

The effects of mesulergine (100 and 200 mu g/kg s.c.), SB 206553 (1 an d 2.5 mg/kg i.p.), RP 62203 (2.5 and 4 mg/kg i.p.) and ritanserin (630 mu g/kg i.p.) were studied on the extracellular concentration of dopa mine (DA) and dihydroxyphenylacetic acid (DOPAC) in the nucleus accumb ens of chloral hydrate-anesthetized rats, using intracerebral microdia lysis. Mesulergine, a non selective serotonin(2c/2B/2A) (5-HT2C/2B/2A) receptor antagonist, significantly increased DA release, which reache d a peak level (+ 20%) 60 min after drug injection and slowly returned back to baseline values. Mesulergine also caused a dose-dependent inc rease in DOPAC outflow. Pretreatment with mesulergine (200 mu g/kg) di d not change the inhibition of DA release induced by apomorphine (100 mu g/kg), whereas it prevented the reduction of DOPAC outflow induced by apomorphine (100 mu g/kg). Administration of SB 206553, a selective blocker of 5-HT2C/2B receptors, dose-dependently increased DA outflow . The dose of 2.5 mg/kg SB 206553 caused a linear increase of DA outpu t which reached a peak (+ 75%) 40 min after injection, while 1 mg/kg i nduced a more gradual increase of DA release which peaked (+/- 54%) 60 min after administration of the drug. Treatment with RP 62203, a sele ctive 5-HT2A receptor antagonist, did not produce any significant effe ct on DA outflow. Administration of ritanserin, a mixed 5-HT2A/2C rece ptor antagonist, did not cause any significant change of DA and DOPAC outflow. Taken together, these data indicate that selective blockade o f 5-HT2C/2B receptor subtypes increases DA release in the rat nucleus accumbens. (C) 1998 Elsevier Science Ltd. All rights reserved.