Increase of dialysate dopamine in the bed nucleus of stria terminalis by clozapine and related neuroleptics

Neuroleptics are known to stimulate dopamine release in neostriatal termina l areas. In the present study we have investigated by brain microdialysis i n freely mo moving mts the effect of typical and atypical neuroleptics on d opamine transmission in tl-le bed nucleus of stria terminalis, a dopamine t erminal area belonging to the limbic system and recently assigned the so-ca lled extended amygdala. Mean basal dialysate dopamine values were 14.3 mole s/20 mu l sample. Dopamine output in dialysates was increased dose-by cloza pine (max + 158%, 248%, and 461% of basal nt 5, 10, and 20 mg/kg LP, respec tively), risperidone (max + 115% and 221% of basal at I and 3 mg/kg IF, res pectively, olanzapine (max + 138% and 235% of basal at 3 and 6 mg/kg IF, re spectively, BIMG 80 (max) 64% and 164% of basal at 3 and 5 mg/kg IF, respec tively, amperozide(max + 110% and 194% of basal at 3 and 6 mg/kg IF, respec tively, The selective dopamine D-4 antagonist L-745,870 increased dialysate dopamine but at rather high closes and not as effectively as clozapine (ma x + + 32%, 89%, and 130% of basal at 2.7, 5.4, and 10.8 mg/kg IF, respectiv ely). The typical neuroleptic haloperidol (0.1 and 0.5 mg/kg SC) and the se lective D-2 antagonist raclopride (0.14, 0.56, and 2.1 mg/kg SC), the serot onergic 5-HT2 antagonist ritanserin (0.5 and 1.5 mg/kg IF), and the adrener gic alpha(1) antagonist prazosin (0.91 and 2.73 mg/kg IP) did not affect di alysate dopamine in the bed nucleus of stria terminalis. Saline (I ml/kg SC or 3 ml/kg IF) did not modify dialysate dopamine. Therefore, atypical neur oleptics share the ability of stimulating dopamine transmission in the bed nucleus of stria terminalis, brit this property is not mimicked by any of t he! drug tested that selectively act on individual receptors among those th at lire affected by atypical neuroleptics These observations raise the poss ibility that the property of increasing dopamine transmission in the bed nu cleus of stria terminalis is the result of combined blockade of dopamine, s erotonin, and noradrenaline re receptors and that might be profile predicti ve of an atypical neuroleptic profile. (C) 1999 American College of Neurops ychopharmacology. Published by Elsevier Science Inc.