Abstract
Rats learned to lever-press when reinforced with response-contingent microinfusions of the dopamine uptake inhibitor nomifensine (1.7 nmol per injection) into the ventro-medial (shell) region of nucleus accumbens septi (NAS). The drug was not effective when similar injections were given either in random relation to lever-pressing, into the more dorso-lateral (core) region of NAS, or into the frontal cortex. Cocaine was also effective in NAS, but considerably less so. These data suggest that response-contingent dopamine uptake blockade within the NAS is sufficient to establish and maintain instrumental response habits.
References
Bozarth MA, Wise RA (1980) Electrolytic microinfusion transducer system: an alternate method of intracranial drug application. J Neurosci Meth 2:273–275
Criswell HE (1977) A simple chronic microinjection system for use with chemitrodes. Pharmacol Biochem Behav 6:237–238
de Wit H, Wise RA (1977) Blockade of cocaine reinforcement in rats with the dopamine receptor blocker pimozide but not with the noradrenergic blockers phentolamine or phenoxybenzamine. Can J Psychol 31:195–203
Ettenberg A, Geist TD (1992) Qualitative and quantitative differences in the operant runway behavior of rats working for cocaine and heroin reinforcement. Pharmacol Biochem Behav 44:191–198
Goeders NE, Smith JE (1983) Cortical dopaminergic involvement in cocaine reinforcement. Science 221:773–775
Goeders NE, Smith JE (1986) Reinforcing properties of cocaine in the medial prefrontal cortex: Primary action on presynaptic dopaminergic terminals. Pharmacol Biochem Behav, 25:191–199
Goeders NE, Smith JE (1993) Intracranial cocaine self-administration into the medial prefrontal cortex increases dopamine turnover in the nucleus accumbens. J Pharmacol Exp Ther 265:592–600
Guerin GF, Goeders NE, Dworkin SI, Smith JE (1984) Intracranial self-administration of dopamine into the nucleus accumbens. Soc Neurosci Abstr 10:1072
Hernandez L, Hoebel BG (1988) Food reward and cocaine increase extracellular dopamine in the nucleus accumbens as measured by microdialysis. Life Sci 42:1705–1712
Hoebel BG, Monaco AP, Hernandez L, Aulisi EF, Stanley BG, Lenard L (1983) Self-injection of amphetamine directly into the brain. Psychopharmacology 81:158–163
Johnson AK, Epstein AN (1975) The cerebral ventricles as the avenue for the dipsogenic action of intracranial angiotensin. Brain Res 86:399–418
Lew R, Vaughan R, Simantov R, Wilson A, Kuhar MJ (1991) Dopamine transporters in the nucleus accumbens and the striatum have different apparent molecular weights. Synapse 8:152–153
Loh EA, Roberts DCS (1990) Break-points on a progressive ratio schedule reinforced by intravenous cocaine increase following depletion of forebrain serotonin. Psychopharmacology 101:262–266
Lyness WH, Friedle NM, Moore KE (1979) Destruction of dopaminergic nerve terminals in nucleus accumbens: effect ond-amphetamine self-administration. Pharmacol Biochem Behav 11:553–556
Martin-Iverson MT, Szostak C, Fibiger HC (1986) 6-Hydroxydopamine lesions of the medial prefrontal cortex fail to influence intravenous self-administration of cocaine. Psychopharmacology 88:310–314
Moghaddam B, Bunney BS (1989) Ionic composition of microdialysis perfusing solution alters the pharmacological responsiveness and basal outflow of striatal dopamine. J Neurochem 53:652–654
Nomikos GG, Damsma G, Wenkstern BA, Fibiger HC (1990) In vivo characterization of locally applied dopamine uptake inhibitors by striatal microdialysis. Synapse 6:106–112
Phillips, GD, Robbins, TW, Everitt, BJ (1994) Bilateral intra-accumbens self-administration ofd-amphetamine: antagonism with intra-accumbens SCH-23390 and sulpiride. Psychopharmacology 114:477–485
Richardson NR, Roberts DCS (1991) Fluoxetine pretreatment reduces breaking points on a progressive ratio schedule reinforced by intravenous cocaine self-administration in the rat. Life Sci 49:833–840
Risner ME, Jones BE (1976) Role of noradrenergic and dopaminergic processes in amphetamine self-administration. Pharmacol Biochem Behav 5:477–482
Risner ME, Jones BE (1980) Intravenous self-administration of cocaine and norcocaine by dogs. Psychopharmacology 71:83–89
Ritz MC, Lamb RJ, Goldberg SR, Kuhar MJ (1987) Cocaine receptors on dopamine transporters are related to self-administration of cocaine. Science 237:1219–1223
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-OHDA lesions of the nucleus accumbens. Pharmacol Biochem Behav 12:781–787
Samanin R, Bernasconi S, Garattini S (1975) The effect of nomifensine on the depletion of brain serotonin and catecholamines induced respectively by fenfluramine and 6-hydroxydopamine. Eur J Pharmacol 34:377–380
Schenk S, Horger BA, Peltier R, Shelton K (1991) Supersensitivity to the reinforcing effects of cocaine following 6-hydroxydopamine lesions to the medial prefrontal cortex in rats. Brain Res 543:227–235
Yokel RA, Wise RA (1975) Increased lever-pressing for amphetamine after pimozide in rats: Implications for a dopamine theory of reward. Science 187:547–549
Yokel RA, Wise RA (1976) Attenuation of amphetamine reinforcement by central dopamine blockade in rats. Psychopharmacology 48:311–318
Zahm DS, Brog JS (1992) On the significance of subterritories in the “accumbens” part of the rat ventral striatum. Neuroscience 50:751–767
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Carlezon, W.A., Devine, D.P. & Wise, R.A. Habit-forming actions of nomifensine in nucleus accumbens. Psychopharmacology 122, 194–197 (1995). https://doi.org/10.1007/BF02246095
Received:
Revised:
Issue Date:
DOI: https://doi.org/10.1007/BF02246095