Effects of cholecystokinin peptides and neurotensin on dopamine release and metabolism in the rostral and caudal part of the nucleus accumbens using intracerebral dialysis in the anaesthetized rat

Abstract

By means of intracerebral microdialysis effects of cholecystokinin peptides and neurotensin administered via the microdialysis probe have been studied on dopamine release and metabolism in the nucleus accumbens and neostriatum of the halothane anaesthetized male rat. Levels of extra cellular dopamine (DA) and its metabolites 3,4 dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) were assessed in nuc. accumbens (rostral and caudal part) using high performance liquid chromatography in combination with electrochemical detection. (1) In the rostral part of the nuc. accumbens CCK-8 (10 and 100 ?M), CCK-33 (100 ?M) but not CCK-4 (10 and 100 ?M) increased the levels of DA in the perfusate without increasing the extracellular levels of DOPAC and HVA. (2) In the caudal nuc. accumbens CCK-8 and CCK-4 in concentrations of 10 ?M and 100 ? M of CCK-33 had no effect on DA release and metabolism, since the extracellular levels of DA, DOPAC and HVA were not changed. (3) In the rostral nuc. accumbens perfusion with 10 ?M of neurotensin but not with any other concentration of neurotensin (0.01, 0.1, 1 and 100 ?M) increased the levels of DA in the extracellular fluid. (4) In the caudal nuc. accumbens a 40 min perfusion with neutrotensin produced a concentration dependent increase of the levels of DA in the perfusate (peak action at 10 ? M) which in this case was associated with increases in the extracellular levels of DOPAC and HVA. (5) By means of receptor autoradiography using (3-[(125)I]iodotyrosyl(3)) neurotensin it was found that a 40 min perfusion with this radioligand in the rostral nuc. accumbens reached a total volume of 0.051 mm(3). The diffusion of the radioligand was limited to the rostral or caudal part of the nuc. accumbens depending upon the site of placement of the dialysis probe. The results indicate the existence of cholecystokinin (CCK) receptors in the rostral nuc. accumbens, which are sensitive to CCK-8 and CCK-33 but not to CCK-4, and which facilitate DA release without producing any detectable increase in DA metabolites. In contrast, such receptors do not appear to play a similar role in the regulation of DA release in the caudal nuc. accumbens, where DA terminals contain CCK-like immunoreactivity. Furthermore, the results indicate that neurotensin receptors exist both in the rostral and caudal nuc. accumbens, where they inter alia enhance the release of DA. In the caudal nuc. accumbens these effects of neurotensin are also associated with an increase of DA metabolites, possibly suggesting that in this region neurotensin receptors may also control DA synthesis.