Effects of long-term haloperidol treatment on the responsiveness of accumbens neurons to cholecystokinin and dopamine: electrophysiological and radioligand binding studies in the rat.
Cholecystokinin (CCK) and dopamine (DA) coexist in a subpopulation of neurons of the ventral tegmental area projecting to the nucleus accumbens. The present experiments were undertaken to determine the effect of acute and long-term administration of haloperidol on the responsiveness of accumbens neurons to microiontophoretic applications of the sulfated cholecystokinin octapeptide (CCK-8S), kainate (KA), and DA and on the density of CCK, D1, and D2 receptors determined by radioautography. Acute administration of haloperidol (1 mg/kg, i.v.) did not modify the neuronal responsiveness to DA and KA but increased that to CCK-8S. Long-term treatment with haloperidol decanoate (4 mg/kg/week, i.m., for 3-5 weeks) induced a marked increase in the responsiveness to CCK-8S, without noticeable change of that to DA and KA. After a 5 week treatment, significant increases in the amounts of CCK and D2 binding were found in the nucleus accumbens, whereas D1 binding parameters remained unchanged. Since long-term haloperidol treatment results in a depolarization inactivation of A10 dopaminergic neurons, these results suggest that, despite the reduced firing activity of mesolimbic dopaminergic neurons induced by the long-term haloperidol treatment, dopamine is still released in an amount sufficient to maintain a normal neuronal responsiveness of postsynaptic accumbens neurons to DA, whereas the release of CCK is possibly decreased to a greater extent, resulting in an enhanced responsiveness of the neurons to this peptide.
Debonnel
G
G
Institut Philippe Pinel de Montréal, Quebec, Canada.
Gaudreau
P
P
Quirion
R
R
de Montigny
C
C
D000818:Animals; D001345:Autoradiography; D002766:Cholecystokinin / Q000494:pharmacology*; D004298:Dopamine / Q000494:pharmacology*; D004594:Electrophysiology; D006220:Haloperidol / Q000494:pharmacology*; D008297:Male; D009474:Neurons / Q000187:drug effects*; D009714:Nucleus Accumbens / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D011919:Rats, Inbred Strains; D011949:Receptors, Cholecystokinin / Q000378:metabolism; D011954:Receptors, Dopamine / Q000378:metabolism; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D012686:Septal Nuclei / Q000187:drug effects*; D013997:Time Factors
D011949:Receptors, Cholecystokinin; D011954:Receptors, Dopamine; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D002766:Cholecystokinin; D006220:Haloperidol; D004298:Dopamine