The role of nucleus accumbens dopamine in responding on a continuous reinforcement operant schedule: A neurochemical and behavioral study

Two experiments were undertaken to investigate the role of nucleus accumbens dopamine (DA) in instrumental lever pressing on a continuous reinforcement (CRF) schedule. Rats trained to press a lever for food reinforcement on a CRF schedule, and food-deprived control rats, were implanted with dialysis probes in the nucleus accumbens. The day after implantation, rats were tested and dialysis samples were assayed for DA and the DA metabolite 3,4-dihydroxyphenylacetic acid (DOPAC). Performance of the lever-pressing task resulted in significant increases in extracellular levels of DA and DOPAC relative to control rats. The increases in extracellular DA were significantly correlated (r = 0.92) with the number of lever press responses committed. In the second experiment, the neurotoxic agent 6-hydroxydopamine was infused directly into the nucleus accumbens to investigate the effects of DA depletion on lever-pressing performance. DA depletion had only a modest effect on the total number of lever presses, and there was a significant effect on total lever presses only on the first test day (third day postsurgery). Analyses also were performed on responding across the 45-min session by breaking down the session into three 15-min periods. There was a significant group x time interaction, with DA-depleted rats showing a significant reduction in the numbers of responses in the first 15-min period, but no significant effects over the second or third 15 min in the session. This initial slowing of response rate was present across all 5 test days. These results indicate that DA release and metabolism increases in rats performing on a CRF schedule, and that DA depletion produces a slowing of initial response rate.

[1]  T. Robbins,et al.  Interactions between the amygdala and ventral striatum in stimulus-reward associations: Studies using a second-order schedule of sexual reinforcement , 1989, Neuroscience.

[2]  K. Spivak,et al.  Effects of pimozide on appetitive behavior and locomotor activity: Dissimilarity of effects when compared to extinction , 1986, Physiology & Behavior.

[3]  J. Salamone The Actions of Neuroleptic Drugs on Appetitive Instrumental Behaviors , 1987 .

[4]  B. Hoebel,et al.  Food reward and cocaine increase extracellular dopamine in the nucleus accumbens as measured by microdialysis. , 1988, Life sciences.

[5]  R. Wise Neuroleptics and operant behavior: The anhedonia hypothesis , 1982, Behavioral and Brain Sciences.

[6]  A. Kelley,et al.  Disappearance of hoarding behavior after 6-hydroxydopamine lesions of the mesolimbic dopamine neurons and its reinstatement with L-dopa. , 1985, Behavioral Neuroscience.

[7]  J. Salamone,et al.  A neurochemical and behavioral investigation of the involvement of nucleus accumbens dopamine in instrumental avoidance , 1993, Neuroscience.

[8]  J. Salamone Dopaminergic involvement in activational aspects of motivation: Effects of haloperidol on schedule-induced activity, feeding, and foraging in rats , 1988, Psychobiology.

[9]  R. Wise,et al.  Neuroleptic-induced "anhedonia" in rats: pimozide blocks reward quality of food. , 1978, Science.

[10]  E. Abercrombie,et al.  Differential Effect of Stress on In Vivo Dopamine Release in Striatum, Nucleus Accumbens, and Medial Frontal Cortex , 1989, Journal of neurochemistry.

[11]  H. Fibiger,et al.  Force requirements in lever-pressing and responding after haloperidol , 1984, Pharmacology Biochemistry and Behavior.

[12]  W. Faustman,et al.  An examination of methodological refinements, clozapine and fluphenazine in the anhedonia paradigm , 1982, Pharmacology Biochemistry and Behavior.

[13]  A. Ettenberg,et al.  Neuroleptic-induced deficits in operant responding for temperature reinforcement , 1985, Pharmacology Biochemistry and Behavior.

[14]  T. Ono,et al.  Neuronal activity in the ventral tegmental area (VTA) during motivated bar press feeding in the monkey , 1987, Brain Research.

[15]  T. Robbins,et al.  Selective disruption of displacement behaviour by lesions of the mesolimbic dopamine system , 1980, Nature.

[16]  R. Wise,et al.  Major attenuation of food reward with performance-sparing doses of pimozide in the rat. , 1978, Canadian journal of psychology.

[17]  T. Robbins,et al.  Cortical, hippocampal, and striatal mediation of schedule-induced behaviors. , 1990, Behavioral neuroscience.

[18]  S. T. Mason,et al.  Pimozide-induced suppression of responding: Evidence against a block of food reward , 1980, Pharmacology Biochemistry and Behavior.

[19]  A. Phillips,et al.  Dopamine and preparatory behavior: II. A neurochemical analysis. , 1989 .

[20]  J. Salamone,et al.  Involvement of nucleus accumbens dopamine in the motor activity induced by periodic food presentation: a microdialysis and behavioral study , 1992, Brain Research.

[21]  A. Phillips,et al.  Role of dopamine in anticipatory and consummatory aspects of sexual behavior in the male rat. , 1991, Behavioral neuroscience.

[22]  Anthony G. Phillips,et al.  Decreased resistance to extinction after haloperidol: Implications for the role of dopamine in reinforcement , 1979, Pharmacology Biochemistry and Behavior.

[23]  G. Di Chiara,et al.  Drugs abused by humans preferentially increase synaptic dopamine concentrations in the mesolimbic system of freely moving rats. , 1988, Proceedings of the National Academy of Sciences of the United States of America.

[24]  T. Robbins,et al.  Involvement of the amygdala in stimulus-reward associations: Interaction with the ventral striatum , 1989, Neuroscience.

[25]  J. Salamone,et al.  Behavioral activation in rats increases striatal dopamine metabolism measured by dialysis perfusion , 1989, Brain Research.

[26]  John D. Salamone,et al.  The role of brain dopamine in response initiation: effects of haloperidol and regionally specific dopamine depletions on the local rate of instrumental responding , 1993, Brain Research.

[27]  T. Robbins,et al.  Effects of 6-hydroxydopamine lesions of the nucleus accumbens septi and olfactory tubercle on feeding, locomotor activity, and amphetamine anorexia in the rat. , 1978, Journal of comparative and physiological psychology.

[28]  B. Scatton,et al.  Tail-pinch stress increases extracellular DOPAC levels (as measured by in vivo voltammetry) in the rat nucleus accumbens but not frontal cortex: antagonism by diazepam and zolpidem , 1987, Brain Research.

[29]  W. Faustman,et al.  Use of operant response duration to distinguish the effects of haloperidol from nonreward , 1981, Pharmacology Biochemistry and Behavior.

[30]  John D. Salamone,et al.  Ventrolateral striatal dopamine depletions impair feeding and food handling in rats , 1993, Pharmacology Biochemistry and Behavior.