Medial prefrontal cortical alpha1 adrenoreceptor modulation of the nucleus accumbens dopamine response to stress in Long-Evans rats.
BACKGROUND
The medial prefrontal cortex (PFC) receives stress-sensitive dopamine (DA) and noradrenergic (NE) projections from the ventral tegmental area and locus coeruleus, respectively, and evidence from various sources point to a complex functional interaction between these two systems. Stress will also stimulate DA transmission in the nucleus accumbens (NAcc), and our previous work has shown that this response is under the indirect inhibitory control of a DA-sensitive mechanism in PFC.


OBJECTIVE
We examined the possibility that the NAcc DA stress response is also modulated by prefrontal cortical NE.


METHODS
We used voltammetry to study in freely behaving rats the effects of local applications of alpha(1) (benoxathian 0.1, 1, 10 nmol), alpha(2) (SKF86466), and beta(1/2) (alprenolol) receptor selective antagonists into the PFC on the NAcc DA response to tail-pinch stress.


RESULTS
The NAcc DA stress response was dose-dependently inhibited by local PFC blockade of alpha(1) receptors. Additional tests revealed, however, that the DA stress response in NAcc is unaffected after local alpha(1) receptor activation with cirazoline. Furthermore, at equivalent doses, neither alpha(2) nor beta(1/2) receptor blockade significantly affected the NAcc DA stress response.


CONCLUSIONS
These data indicate that stress-induced activation of subcortical DA transmission is modulated by the NE input to PFC acting at alpha(1) receptors. They suggest that, under normal circumstances, this system exerts a facilitatory or enabling influence on the NAcc DA stress response.
Nicniocaill
Brid
B
Douglas Hospital Research Center, Department of Psychiatry, McGill University, 6875 LaSalle Blvd, Montréal (Verdun), H4H 1R3, Québec, Canada.
Gratton
Alain
A
D018674:Adrenergic Antagonists / Q000494:pharmacology; D058668:Adrenergic alpha-1 Receptor Antagonists; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000526:Alprenolol / Q000494:pharmacology; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001552:Benzazepines / Q000494:pharmacology; D004298:Dopamine / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D007093:Imidazoles / Q000494:pharmacology; D008297:Male; D009638:Norepinephrine / Q000378:metabolism*; D009714:Nucleus Accumbens / Q000378:metabolism*; D010075:Oxathiins / Q000494:pharmacology; D011199:Potentiometry / Q000379:methods; D017397:Prefrontal Cortex / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D020318:Rats, Long-Evans; D018340:Receptors, Adrenergic, alpha-1 / Q000378:metabolism*; D013315:Stress, Psychological / Q000378:metabolism*; D013997:Time Factors
D018674:Adrenergic Antagonists; D058668:Adrenergic alpha-1 Receptor Antagonists; D000316:Adrenergic alpha-Agonists; D001552:Benzazepines; D007093:Imidazoles; D010075:Oxathiins; D018340:Receptors, Adrenergic, alpha-1; D000526:Alprenolol; C050877:benoxathian; C014282:cirazoline; D004298:Dopamine; D009638:Norepinephrine; C039139:benalfocin