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 terminal areas. In the present study, we have investigated by brain microdialysis in freely moving rats the effect of typical and atypical neuroleptics on dopamine transmission in the 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 f moles/20 microliters sample. Dopamine output in dialysates was increased dose-dependently by clozapine (max + 158%, 298%, and 461% of basal at 5, 10, and 20 mg/kg i.p., respectively), risperidone (max + 115% and 221% of basal at 1 and 3 mg/kg i.p., respectively), olanzapine (max + 138% and 235% of basal at 3 and 6 mg/kg i.p., respectively), BIMG 80 (max + 64% and 164% of basal at 3 and 5 mg/kg i.p., respectively), amperozide (max + 110% and 194% of basal at 3 and 6 mg/kg i.p., respectively). The selective dopamine D4 antagonist L-745,870 increased dialysate dopamine but at rather high doses and not as effectively as clozapine (max + 32%, 89%, and 130% of basal at 2.7, 5.4, and 10.8 mg/kg i.p., respectively). The typical neuroleptic haloperidol (0.1 and 0.5 mg/kg s.c.) and the selective D2 antagonist raclopride (0.14, 0.56, and 2.1 mg/kg s.c.), the serotonergic 5-HT2 antagonist ritanserin (0.5 and 1.5 mg/kg i.p.), and the adrenergic alpha 1 antagonist prazosin (0.91 and 2.73 mg/kg i.p.) did not affect dialysate dopamine in the bed nucleus of stria terminalis. Saline (1 ml/kg s.c. or 3 ml/kg i.p.) did not modify dialysate dopamine. Therefore, atypical neuroleptics share the ability of stimulating dopamine transmission in the bed nucleus of stria terminalis, but this property is not mimicked by any of the drug tested that selectively act on individual receptors among those that are 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 receptors and that might be predictive of an atypical neuroleptic profile.
Carboni
E
E
Department of Toxicology, University of Cagliari, Italy.
Rolando
M T
MT
Silvagni
A
A
Di Chiara
G
G
D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D001569:Benzodiazepines; D003024:Clozapine / Q000494:pharmacology*; D004298:Dopamine / Q000378:metabolism*; D007700:Kinetics; D008297:Male; D017551:Microdialysis; D000077152:Olanzapine; D010879:Piperazines / Q000494:pharmacology; D010890:Pirenzepine / Q000031:analogs & derivatives / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018967:Risperidone / Q000494:pharmacology; D012686:Septal Nuclei / Q000187:drug effects / Q000378:metabolism*
D014150:Antipsychotic Agents; D010879:Piperazines; C049058:amperozide; D001569:Benzodiazepines; D010890:Pirenzepine; D003024:Clozapine; D018967:Risperidone; D000077152:Olanzapine; D004298:Dopamine