Blockade of D-1 dopamine receptors in the medial prefrontal cortex produces delayed effects on pre- and postsynaptic indices of dopamine function in the nucleus accumbens.
The present experiments assessed the acute and delayed effects of D-1 dopamine (DA) receptor blockade in the medial prefrontal cortex (mPFC) on pre- and postsynaptic indices of DA neurotransmission in the nucleus accumbens (N.Acc). Different groups of rats received intra-mPFC injections of saline (control animals) or the D-1 DA receptor antagonist SCH-23390 (0.25 microgram/side). Acutely, intra-mPFC injections of this antagonist did not affect spontaneous locomotion but significantly increased the locomotion induced by intra-N.Acc. amphetamine (1.5 micrograms/side), in agreement with our earlier findings [Vezina et al. (1991) Eur. J. Neurosci., 3:1001-1007]. When tested two days post-injection, however, mPFC-SCH-23390 preexposed animals showed lower levels of locomotor activity than Control animals in response to intra-N.Acc. injections of amphetamine. This effect was not observed in other animals preexposed two days earlier to mPFC injections of amphetamine (2.5 micrograms/side) or the D-2 DA receptor antagonist sulpiride (1.0 microgram/side). Animals preexposed two days earlier to mPFC SCH-23390 also showed higher levels of locomotor activity (+98%) when tested with intra-N.Acc. injections of the D-1 DA receptor agonist SKF-38393 (1.0 microgram/side) and a 36% increase in maximal DA-sensitive adenylate cyclase activity in comparison to Control animals. These effects were no longer observed in animals tested seven days following the mPFC SCH-23390 injections. These results demonstrate delayed actions resulting from cortical D-1 DA receptor blockade.(ABSTRACT TRUNCATED AT 250 WORDS)
Vezina
P
P
Chaire de Neuropharmacologie, INSERM U. 114, Collège de France, Paris.
Blanc
G
G
Glowinski
J
J
Tassin
J P
JP
D000262:Adenylyl Cyclases / Q000378:metabolism; D000661:Amphetamine / Q000494:pharmacology; D000818:Animals; D001552:Benzazepines / Q000494:pharmacology; D004058:Diffusion; D004298:Dopamine / Q000494:pharmacology / Q000502:physiology*; D018492:Dopamine Antagonists; D007267:Injections; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D009714:Nucleus Accumbens / Q000502:physiology*; D017397:Prefrontal Cortex / Q000378:metabolism*; D017729:Presynaptic Terminals / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011954:Receptors, Dopamine; D013569:Synapses / Q000502:physiology*; D013997:Time Factors
D001552:Benzazepines; D018492:Dopamine Antagonists; D011954:Receptors, Dopamine; C027460:dopamine-I receptor; D000661:Amphetamine; D000262:Adenylyl Cyclases; D004298:Dopamine