The dopaminergic hyper-responsiveness of the shell of the nucleus accumbens is hormone-dependent.
The dopaminergic projection to the shell of the nucleus accumbens is the most reactive to stress, reward and drugs of abuse and this subregion of the nucleus accumbens is also considered a target of therapeutic effects of atypical antipsychotic drugs (APD). In this report we show, by means of in vivo microdialysis and Fos immunohistochemistry, that the hyper-responsiveness which characterizes the dopaminergic transmission to the shell is dependent on glucocorticoid hormones. In Sprague-Dawley rats, after suppression of endogenous glucocorticoids by adrenalectomy, extracellular dopamine levels selectively decreased in the shell, whilst they remained unchanged in the core. This effect was observed in basal conditions, after a mild stress (vehicle injection), as well as after subcutaneous administration of morphine (2 mg/kg, s.c. ) or intraperitoneal injection of cocaine (15 mg/kg, i.p.). The decrease in dopamine observed in the shell had a postsynaptic impact, as shown by less induction of Fos-like proteins selectively in the shell in response to cocaine. However, the induction of Fos-like proteins by the full D1 agonist SKF82958 (1.5 mg/kg, i.p.) remained unchanged after adrenalectomy, suggesting that the changes in Fos expression after cocaine injection were likely to depend on changes in extracellular dopamine levels rather than on changes in postsynaptic sensitivity to dopamine. The effects of adrenalectomy were glucocorticoid-specific given that they were prevented by corticosterone treatment. This anatomical specificity in the control of neuronal activity by a hormonal input highlights the role of steroid hormones in shaping the functional activity of the brain.
Barrot
M
M
Psychobiologie des Comportements Adaptatifs, INSERM U259, Université Victor Segalen Bordeaux2, Domaine de Carreire, Rue Camille Saint-Saëns, 33077 Bordeaux Cedex, France.
Marinelli
M
M
Abrous
D N
DN
Rougé-Pont
F
F
Le Moal
M
M
Piazza
P V
PV
D000315:Adrenalectomy; D000818:Animals; D001552:Benzazepines / Q000494:pharmacology; D003042:Cocaine / Q000494:pharmacology; D003345:Corticosterone / Q000494:pharmacology; D004298:Dopamine / Q000378:metabolism / Q000502:physiology*; D018491:Dopamine Agonists / Q000494:pharmacology; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology; D005938:Glucocorticoids / Q000494:pharmacology / Q000502:physiology*; D007150:Immunohistochemistry; D008297:Male; D017551:Microdialysis; D009714:Nucleus Accumbens / Q000033:anatomy & histology / Q000378:metabolism / Q000502:physiology*; D016760:Proto-Oncogene Proteins c-fos / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D017447:Receptors, Dopamine D1 / Q000819:agonists; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology
D001552:Benzazepines; D018491:Dopamine Agonists; D018765:Dopamine Uptake Inhibitors; D005938:Glucocorticoids; D016760:Proto-Oncogene Proteins c-fos; D017447:Receptors, Dopamine D1; C071262:SK&F 82958; D003042:Cocaine; D004298:Dopamine; D003345:Corticosterone