|Reference : Acute Amphetamine-Induced Subsensitivity of A10 Dopamine Autoreceptors in Vitro|
|Scientific journals : Article|
|Human health sciences : Pharmacy, pharmacology & toxicology|
|Acute Amphetamine-Induced Subsensitivity of A10 Dopamine Autoreceptors in Vitro|
|Seutin, Vincent [Université de Liège - ULg > Département des sciences biomédicales et précliniques > Pharmacologie >]|
|Verbanck, Paul [> > > >]|
|Massotte, Laurent [Université de Liège - ULg > Département des sciences biomédicales et précliniques > Département des sciences biomédicales et précliniques >]|
|Dresse, Albert [Université de Liège - ULg > Services généraux (Faculté de médecine) > Relations académiques et scientifiques (Médecine) >]|
|[en] Extracellular recordings were obtained from spontaneously active, presumed dopamine (DA) neurons of the ventral tegmental area (VTA) of the rat in a slice preparation. Bath-applied (+)-amphetamine (AMPH) (1-30 microM) induced a concentration-dependent decrease in the firing rate of these neurons, which tended to saturate with the highest concentrations used (n = 11). This inhibitory effect was dependent on the activation of D2 receptors since it was reversed by the D2 antagonist sulpiride (n = 8). However, the most striking effect of AMPH was the induction of a prominent subsensitivity of DA autoreceptors: whereas in 18 out of 20 control neurons, the D2 agonist BHT 920 (100 nM) produced a rapid and complete inhibition of the firing, this was observed in none out of 11 neurons 10 min after the end of the application of AMPH (1-30 microM) (P less than 0.001). In these cells, the mean percent inhibition produced by BHT 920 was only 47 +/- 8%. This subsensitivity remained unchanged after 20 min and declined after one hour. This effect was specific, since the sensitivity of GABAB receptors to baclofen (500 nM-1 microM) was not modified by the application of AMPH (n = 12). These results suggest that AMPH-induced DA autoreceptor subsensitivity can be produced acutely and may be the first step in a cascade of events leading to behavioral sensitization to this compound.|
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