Neurotensin and cholecystokinin octapeptide control synergistically dopamine release and dopamine D₂ receptor affinity in rat neostriatum

Combined perfusion of the neostriatum with 1 nM of cholecystokinin octapeptide (CCK-8) and 0.01, 0.1 or 1 nM of neurotensin was done in the halothane-anesthetized rat after systemic apomorphine treatment (0.05 mg/kg, s.c.). Neurotensin (1 nM) plus CCK-8 (1 nM) effectively counteracted the apomorphine-induced inhibition of neostriatal perfusate levels of dopamine (DA). With a constant concentration of CCK-8 (1 nM), the apomorphine-induced inhibition of DA release was counteracted dose relatedly by neurotensin in concentrations of 0.01, 0.1 and 1 nM. The results of binding experiments demonstrated that threshold concentrations of CCK-8 and neurotensin significantly increased the K_D values of the high-affinity D₂ receptors without significant alterations in the low-affinity D₂ receptors or in the proportion of D₂ receptors in the high-affinity state. Thus, neurotensin and CCK receptors may regulate synergistically, via intramembrane interactions with the D₂ receptors, the binding characteristics and the signal transduction of D₂ autoreceptors in the neostriatum. The combined presence of very low concentrations of CCK-8 and neurotensin in the extracellular fluid may be sufficient to regulate D₂ receptor transduction, underlining the important role of these peptide receptor interactions with the D₂ receptors.