Abstract
Cholecystokinin (CCK) and dopamine (DA) coexist in both cell body and terminal areas of a mesolimbic pathway that projects from the ventral tegmental area (VTA) to the nucleus accumbens (N ACC). Autoradiography reveals extensive CCK binding sites in the N ACC, but not in the VTA. However, iontophoresis of CCK into the VTA results in activation or deactivation of DA neuronal firing rates, and bursting activity (depending on the dose of CCK administered). CCK could have neuromodulatory effects on mesolimbic DA neurons. In two studies, behavioral effects of infusions of CCK into the VTA were examined in the conditioned place preference (CPP) paradigm. The CPP paradigm is a behavioral test used to assess reinforcement induced by drug administration. Drugs with reinforcing properties can condition preferences for novel environments. CCK infusions into the VTA (0.0, 0.04, 0.4, and 4.0 ng/cannula) potentiated amphetamine CPPs in a dose-dependent linear manner. CCK infusions by themselves did not have significant effects in the CPP paradigm. Results indicate a neuromodulatory role for CCK on the neuronal mechanisms that mediate the reinforcing effects of amphetamine. Results also implicate sites of action for CCK in the VTA.
References
Altar CA, Boyar WC, Oei E, Wood PL (1988) Cholecystokinin attenuates basal and drug-induced increases of limbic and striatal dopamine release. Brain Res 460:76–82
Bhoola KD, Dawbarn D, O'Shaughnessy C, Pycock CJ (1982) Modulation of dopamine receptor activation by the neuropeptides VIP and CCK. Proc Scand Br Pharmacol Soc, C.45(July)
Blumstein LK, Crawley JN, Davis LG, Baldino F Jr (1987) Neuropeptide modulation of apomorphine-induced stereotyped behavior. Brain Res 404:293–300
Crawley JN (1985) Cholecystokinin potentiation of dopamine-mediated behaviors in the nucleus accumbens. Ann NY Acad Sci 448:283–292
Crawley JN (1988) Cholecystokinin potentiates dopamine-induced hypolocomotion in the ventral tegmental area of the rat. Soc Neurosci Abstr 14:291
Crawley JN, Hommer DW, Skirboll LR (1985) Topographical analysis of N ACC sites at which cholecystokinin potentiates dopamine-induced hyperlocomotion in the rat. Brain Res 335:337–341
Freeman AS, Bunney BS (1987) Activity of A9 and A10 dopaminergic neurons in unrestrained rats: further characterization and effects of apomorphine and cholecystokinin. Brain Res 405:46–55
Fuxe K, Andersson K, Locatelli V, Agnati LF, Hokfelt T, Skirboll L, Mutt V (1980) Cholecystokinin peptides produce marked reduction of dopamine turnover in discrete areas in the rat brain following intraventricular injection. Eur J Pharmacol 67:329–331
Gaito J (1965) Unequal intervals and unequal n in trend analyses. Psychol Bull 63:125–127
Hoebel BG, Aulisi E (1984) Cholecystokinin self-injection in the nucleus accumbens and block with proglumide. Soc Neurosci Abstr 10:652
Hokfelt T, Skirboll L, Rehfeld JF, Goldstein M, Markey K, Dann O (1980a) A subpopulation of a mesencephalic dopamine neuron projection to limbic areas contains a cholecystokinin-like peptide. Evidence from immunohistochemistry combined with retrograde tracing. Neuroscience 5:2093–2124
Hokfelt T, Rehfeld JF, Skirboll L, Ivemark B, Goldstein M, Markey K (1980b) Evidence for coexistence of dopamine and CCK in mesolimbic neurons. Nature 285:476–478
Kaltwasser MT, Crawley JN (1987) Oxytocin and cholecystokinin induce grooming behavior in the ventral tegmentum of the rat. Brain Res 426:1–7
Katsuura G, Hsiao S, Itoh S (1984) Cholecystokinin tetrapeptide, proglumide and open-field behavior in rats. Life Sci 34:2165–2168
Kirk RE (1982) Orthogonal coefficients for unequal intervals and unequal n's. In: Brooks, Cole (eds) Experimental design. Procedures for the behavioral sciences (2nd edn) Monterey, California, pp 773–777
Lewis D (1960) Goodness of fit and trend differences. In: Quantitative methods in psychology, McGraw-Hill, New York, pp 407–409
Lyness WH, Friedle NM, Moore KE (1979) Destruction of dopaminergic nerve terminals in nucleus accumbens: effect on d-amphetamine self-administration. Pharmacol Biochem Behav 11:553–556
Mashal RD, Owen F, Deakin JFW, Poulter M (1983) The effects of cholecystokinin on dopaminergic mechanisms in rat striatum. Brain Res 277:375–376
Pellegrino L, Pellegrino A, Cushman A (1979) A stereotaxic atlas of the rat brain. Plenum Press, New York
Phillips AG, Blaha CD, Fibiger HC, Lane RF (1988) Interactions between mesolimbic dopamine neurons, cholecystokinin, and neurotensin: evidence using in vivo voltammetry. Ann NY Acad Sci 537:347–361
Roberts DCS, Corcoran ME, Fibiger HC (1977) On the role of ascending catecholaminergic systems in intravenous self-administration of cocaine. Pharmacol Biochem Behav 6:615–620
Roberts DCS, Koob GF, Klonoff P, Fibiger HC (1980) Extinction and recovery of cocaine self-administration following 6-hydroxydopamine lesions of the nucleus accumbens. Pharmacol Biochem Behav 12:781–787
Skirboll LR, Grace AA, Hommer DW, Rehfeld J, Goldstein M, Hokfelt T, Bunney BS (1981) Peptide-monoamine coexistence: studies of the actions of cholecystokinin-like peptide on the electrical activity of midbrain dopamine neurons. Neuroscience 6:2111–2124
Spyraki C, Fibiger HC, Phillips AG (1982) Dopaminergic substrates of amphetamine-induced place preference conditioning. Brain Res 253:185–193
Vaccarino FJ, Koob GF (1984) Microinjections of nanogram amounts of sulfated cholecystokinin octapeptide into the rat N ACC attenuates brain stimulation reward. Neurosci Lett 52:61–66
Van Dijk A, Gillessen D, Mohler H, Richards JG (1981) Autoradiographical localization of cholecystokinin-receptor binding in rat brain and pancreas in vitro using 3H-CCK-8 as radioligand. Proc Br Pharmacol Soc 122:21 (Sept)
Van Dijk A, Richards JG, Trzeciak A, Gillessen D, Mohler H (1984) Cholecystokinin receptors biochemical demonstration and autoradiographical localization in rat brain and pancreas using [3H]cholecystokinin 8 as radioligand. J Neurosci 4:1021–1033
Voigt MM, Wang RY (1984) In vivo release of dopamine in the nucleus accumbens of the rat: modulation by cholecystokinin. Brain Res 296:189–193
Voigt MM, Wang RY, Westfall TC (1986) Cholecystokinin octapeptides alter the release of endogenous dopamine from the rat N ACC in vitro. J Pharmacol Exp Ther 237:147–153
Zetler G (1980) Effects of cholecystokinin-like peptides on rearing activity and hexobarbital-induced sleep. Eur J Pharmacol 66:137–139
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Pettit, H.O., Mueller, K. Infusions of cholecystokinin octapeptide into the ventral tegmental area potentiate amphetamine conditioned place preferences. Psychopharmacology 99, 423–426 (1989). https://doi.org/10.1007/BF00445571
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DOI: https://doi.org/10.1007/BF00445571