Stimulation of in vivo dopamine transmission in the bed nucleus of stria terminalis by reinforcing drugs.

Drugs of abuse preferentially increase dopamine transmission in the shell of the nucleus accumbens. This area is considered as a transition between the striatum and the extended amygdala a complex neural system that includes the central amygdala and the bed nucleus of stria terminalis, areas that, like the nucleus accumbens shell, are heavily innervated by mesolimbic dopamine neurons originating in the ventral tegmental area. Given the anatomical and neurochemical relationships and similarities with the nucleus accumbens shell it was of interest to investigate whether the dopamine transmission of the bed nucleus of stria terminalis shares with the accumbens shell the peculiar responsiveness to drugs of abuse. To this end we studied by microdialysis with concentric probes, the effect of drugs of abuse on extracellular dopamine in the bed nucleus of stria terminalis. We report that morphine, nicotine, cocaine, ethanol, and the selective dopamine uptake inhibitor GBR 12909 increase effectively and dose dependently extracellular dopamine in the bed nucleus of stria terminalis. These results indicate that the bed nucleus of stria terminalis shares with the nucleus accumbens shell a peculiar sensitivity to the dopamine stimulant actions of drugs of abuse.

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.