Role of the dopaminergic system of the brain in the effects of glucocorticoid hormones.
The conditioned reinforcement properties of the synthetic glucocorticoid dexamethasone and the possible mechanisms of its action were studied using a conditioned place preference response. On test day 1, male Wistar rats were placed in a two-chamber apparatus and the time spent in each sector was measured for 10 min. Over the next six days, combinations of one of the chambers with administration of agents (reinforcement) were presented using injections of dexamethasone in one sector and injections of physiological saline in the other sector on alternate days. After combinations of dexamethasone (0.25-0.77 mg/kg, i.p.) with the non-preferred sector, rats showed dose-dependent place preference on test day 2; however, when dexamethasone was combined with the initially preferred sector, animals given dexamethasone at a dose of 0.75 mg/kg showed only a slight level of place avoidance. Subthreshold doses of phenamine (0.25 mg/kg) given alone had no effect; however, when given on a background of dexamethasone (0.25 mg/kg), phenamine evoked a place preference response in rats lacking an initial place preference for one sector. Administration of dexamethasone alone (0.25 mg/kg) in these conditions did not induce place preference. Administration of the dopamine D2 receptor antagonist sulpiride (20 mg/kg) 30 min before combinations of dexamethasone (0.25 mg/kg) with the non-preferred sector completely prevented the acquisition of place preference. Administration of the D1 dopamine receptor antagonist SCH23390 (0.05 mg/kg) had no effect on the acquisition of conditioned preference. These results provide evidence for the involvement of D2 receptors in conditioned place preference induced by dexamethasone.
Lebedev
A A
AA
Institute of Experimental Medicine, Russian Academy of Medical Sciences, 12 Academician Pavlov Street, 197376 St. Petersburg, Russia.
Gurkovskaya
O V
OV
Nozdrachev
A D
AD
Shabanov
P D
PD
D000661:Amphetamine / Q000494:pharmacology; D000818:Animals; D001552:Benzazepines / Q000494:pharmacology; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D003216:Conditioning, Operant / Q000502:physiology; D003907:Dexamethasone / Q000494:pharmacology; D004298:Dopamine / Q000378:metabolism* / Q000502:physiology; D018492:Dopamine Antagonists / Q000494:pharmacology; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule / Q000662:veterinary; D004347:Drug Interactions; D005938:Glucocorticoids / Q000032:analysis / Q000494:pharmacology*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D011930:Reaction Time / Q000187:drug effects; D017447:Receptors, Dopamine D1 / Q000502:physiology*; D017448:Receptors, Dopamine D2 / Q000502:physiology*; D012054:Reinforcement, Psychology; D013469:Sulpiride / Q000494:pharmacology
D001552:Benzazepines; D018492:Dopamine Antagonists; D018765:Dopamine Uptake Inhibitors; D005938:Glucocorticoids; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D013469:Sulpiride; D003907:Dexamethasone; D000661:Amphetamine; D004298:Dopamine