Neuroleptics are known to stimulate dopamine release in neostriatal terminal areas. In the present study we have investigated by brain microdialysis in freely mo moving mts the effect of typical and atypical neuroleptics on dopamine transmission in tl-le bed nucleus of stria terminalis, a dopamine terminal area belonging to the limbic system and recently assigned the so-called extended amygdala. Mean basal dialysate dopamine values were 14.3 moles/20 mu l sample. Dopamine output in dialysates was increased dose-by clozapine (max + 158%, 248%, and 461% of basal nt 5, 10, and 20 mg/kg LP, respectively), risperidone (max + 115% and 221% of basal at I and 3 mg/kg IF, respectively, olanzapine (max + 138% and 235% of basal at 3 and 6 mg/kg IF, respectively, BIMG 80 (max) 64% and 164% of basal at 3 and 5 mg/kg IF, respectively, amperozide(max + 110% and 194% of basal at 3 and 6 mg/kg IF, respectively, The selective dopamine D-4 antagonist L-745,870 increased dialysate dopamine but at rather high closes and not as effectively as clozapine (max + + 32%, 89%, and 130% of basal at 2.7, 5.4, and 10.8 mg/kg IF, respectively). The typical neuroleptic haloperidol (0.1 and 0.5 mg/kg SC) and the selective D-2 antagonist raclopride (0.14, 0.56, and 2.1 mg/kg SC), the serotonergic 5-HT2 antagonist ritanserin (0.5 and 1.5 mg/kg IF), and the adrenergic alpha(1) antagonist prazosin (0.91 and 2.73 mg/kg IP) did not affect dialysate 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 neuroleptics share the ability of stimulating dopamine transmission in the bed nucleus of stria terminalis, brit this property is not mimicked by any of the! drug tested that selectively act on individual receptors among those that lire affected by atypical neuroleptics These observations raise the possibility that the property of increasing dopamine transmission in the bed nucleus of stria terminalis is the result of combined blockade of dopamine, serotonin, and noradrenaline re receptors and that might be profile predictive of an atypical neuroleptic profile. (C) 1999 American College of Neuropsychopharmacology.
Increase of dialysate dopamine in the bed nucleus of stria terminalis by clozapine and related neuroleptics
CARBONI, EZIO;SILVAGNI, ALESSANDRA;DI CHIARA, GAETANO
2000-01-01
Abstract
Neuroleptics are known to stimulate dopamine release in neostriatal terminal areas. In the present study we have investigated by brain microdialysis in freely mo moving mts the effect of typical and atypical neuroleptics on dopamine transmission in tl-le bed nucleus of stria terminalis, a dopamine terminal area belonging to the limbic system and recently assigned the so-called extended amygdala. Mean basal dialysate dopamine values were 14.3 moles/20 mu l sample. Dopamine output in dialysates was increased dose-by clozapine (max + 158%, 248%, and 461% of basal nt 5, 10, and 20 mg/kg LP, respectively), risperidone (max + 115% and 221% of basal at I and 3 mg/kg IF, respectively, olanzapine (max + 138% and 235% of basal at 3 and 6 mg/kg IF, respectively, BIMG 80 (max) 64% and 164% of basal at 3 and 5 mg/kg IF, respectively, amperozide(max + 110% and 194% of basal at 3 and 6 mg/kg IF, respectively, The selective dopamine D-4 antagonist L-745,870 increased dialysate dopamine but at rather high closes and not as effectively as clozapine (max + + 32%, 89%, and 130% of basal at 2.7, 5.4, and 10.8 mg/kg IF, respectively). The typical neuroleptic haloperidol (0.1 and 0.5 mg/kg SC) and the selective D-2 antagonist raclopride (0.14, 0.56, and 2.1 mg/kg SC), the serotonergic 5-HT2 antagonist ritanserin (0.5 and 1.5 mg/kg IF), and the adrenergic alpha(1) antagonist prazosin (0.91 and 2.73 mg/kg IP) did not affect dialysate 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 neuroleptics share the ability of stimulating dopamine transmission in the bed nucleus of stria terminalis, brit this property is not mimicked by any of the! drug tested that selectively act on individual receptors among those that lire affected by atypical neuroleptics These observations raise the possibility that the property of increasing dopamine transmission in the bed nucleus of stria terminalis is the result of combined blockade of dopamine, serotonin, and noradrenaline re receptors and that might be profile predictive of an atypical neuroleptic profile. (C) 1999 American College of Neuropsychopharmacology.
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