Acute amphetamine-induced subsensitivity of A10 dopamine autoreceptors in vitro.
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.
Laboratory of Pharmacology, University of Liège, Belgium.
V
V
Seutin
P
P
Verbanck
L
L
Massotte
A
A
Dresse
D000661:Amphetamine / Q000494:pharmacology*; D000818:Animals; D001418:Baclofen / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D009994:Osmolar Concentration; D051381:Rats; D011919:Rats, Inbred Strains; D011954:Receptors, Dopamine / Q000187:drug effects* / Q000378:metabolism; D013681:Tegmentum Mesencephali / Q000378:metabolism
D011954:Receptors, Dopamine; D000661:Amphetamine; D001418:Baclofen