Biomedical subjects

M S Cousins

Publications and source records attributed to M S Cousins.

25 records · Page 2Linked to original sources

PubMed1994

Anhedonia or anergia? Effects of haloperidol and nucleus accumbens dopamine depletion on instrumental response selection in a T-maze cost/benefit procedure.

Two experiments were conducted to study the role of dopamine in the performance of a novel cost/benefit procedure. Rats were trained on a T-maze task in which one arm contained a high reinforcement density (4 x 45 mg Bioserve pellets) and the other arm contained a low reinforcement density (2 x 45 mg pellets). Different groups of rats were trained either with unobstructed access to both arms from the start area, or under a condition in which a large vertical barrier (44 cm) was placed in the arm that contained the high density of food reinforcement. In the first experiment, rats trained under each procedure received injections of 0.1 mg/kg haloperidol and tartaric acid vehicle as a control procedure. Analysis of variance indicated that there was a significant effect of the barrier on maze arm choice, a significant effect of haloperidol, and a significant drug x barrier interaction. Haloperidol did not affect arm choice in rats tested without the barrier present, but this drug significantly reduced the number of selections of the arm with high reinforcement density when the barrier was present. In the second experiment, groups of rats were trained as described above, and then received intraaccumbens injections of 6-hydroxydopamine or ascorbate vehicle. Nucleus accumbens dopamine depletions produced by 6-hydroxydopamine decreased the number of selections of the arm with high reinforcement density when the barrier was present, but had no effect on arm choice when the barrier was not present.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1994

Pharmacological characterization of performance on a concurrent lever pressing/feeding choice procedure: effects of dopamine antagonist, cholinomimetic, sedative and stimulant drugs.

This experiment was undertaken to provide a pharmacological characterization of performance on a task involving food-related instrumental and consummatory behavior. Rats were tested in an operant chamber in which there was a choice between pressing a lever to receive a preferred food (Bioserve pellets) or approaching and consuming a less-preferred food (Lab Chow). The lever pressing schedule was a fixed ratio 5 (FR5). Rats usually pressed the lever at high rates to obtain the preferred food, and typically ate little of the lab chow even though it was freely available in the chamber concurrently with the lever pressing schedule. Previous work has shown that injection of dopamine (DA) antagonists, or depletion of DA in the nucleus accumbens, caused a substantial shift in behavior such that lever pressing was reduced but chow consumption increased. In the present study it was shown that the DA antagonist haloperidol decreased lever pressing and increased chow consumption at doses of 0.1 and 0.15 mg/kg. The D1 antagonist SCH 23390 (0.05, 0.1 and 0.15 mg/kg) and the non-selective DA antagonist cis-flupenthixol (0.3 and 0.45 mg/kg) decreased lever pressing and produced substantial increases in chow consumption. The D2 antagonist sulpiride decreased lever pressing, but produced only slight increases in chow intake at the highest dose. Pentobarbital reduced lever pressing and increased chow consumption at 10.0 mg/kg. The muscarinic agonist pilocarpine produced dose-related decreases in lever pressing, but failed to increase chow consumption. Amphetamine produced dose-related decreases in both lever pressing and chow consumption.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1994

Nucleus accumbens dopamine release increases during instrumental lever pressing for food but not free food consumption.

This experiment was undertaken to investigate the role of nucleus accumbens dopamine (DA) in instrumental and consummatory responses for food. In vivo microdialysis methods were used to study DA release and metabolism in the nucleus accumbens of behaving rats. Four behavioral conditions were used: performance on a fixed ratio 5 (FR 5) schedule of food reinforcement, consumption of Bioserve food pellets, consumption of laboratory chow, and food deprivation control. Groups of rats that were previously exposed to these conditions were implanted with dialysis probes in the nucleus accumbens and tested the day after implantation. The rats that pressed a lever on a FR 5 schedule showed significant increases in extracellular DA and DA metabolites compared to food-deprived control rats. In further analyses, rats that responded on the FR5 schedule were divided into three groups based upon their response rates. The rats with low response rates did not significantly differ from control rats, whereas rats with medium and high rates of responding showed significant increases in DA release relative to the control group. Rats that received massed presentation of food pellets or laboratory chow consumed large quantities of food, but showed no significant increases in DA release. This experiment demonstrated that performance of lever pressing behavior is accompanied by an increase in accumbens DA release and metabolism, and that DA release in nucleus accumbens is more closely related to the performance of highly active instrumental responses than it is to consumption of large quantities of food.

3,4-Dihydroxyphenylacetic Acid↗

PubMed1994

Nucleus accumbens dopamine depletions in rats affect relative response allocation in a novel cost/benefit procedure.

Rats were tested on days 1, 3, and 5 of a 5-day test week in an operant chamber in which they could either lever press on a fixed-ratio 5 (FR5) schedule to obtain food pellets (Bioserve) or approach and consume lab chow that was also available in the chamber (Teklad Premier). Rats typically pressed at high rates to obtain the food pellets and ate little of the lab chow. On days 2 and 4 of each week lab chow was not concurrently available, and rats could only lever press on the FR5 schedule for pellets to obtain food. Dopamine depletions produced by intraaccumbens injections of the neurotoxic agent 6-hydroxydopamine produced a dramatic decrease in lever pressing and increase in chow consumption on days when lab chow was available. Lever pressing was not significantly reduced in dopamine-depleted rats on days when chow was not available, although there was a significant correlation between lever pressing and accumbens dopamine levels. These results suggest that nucleus accumbens dopamine depletions do not produce a general deficit in food motivation. Moreover, accumbens dopamine depletions do not appear to produce severe deficits in fine motor control that impair the execution of individual motor acts involved in lever pressing. Rather, the present results are consistent with the notion that accumbens dopamine sets constraints upon which food-related response is selected in a particular situation, and that these depletions alter the relative allocation of food-related responses.

Animals↗

PubMed1993

The role of brain dopamine in response initiation: effects of haloperidol and regionally specific dopamine depletions on the local rate of instrumental responding.

Two experiments were undertaken to investigate dopaminergic involvement in the local rate of responding on a fixed ratio 5 (FR5) instrumental lever pressing schedule. Rats were trained to press a lever for food reinforcement on a FR5 schedule, and a computer program was used to record the interresponse time (IRT) for each response. The IRT is the time between each lever pressing response, which is equal to the reciprocal of the local response rate. After several weeks of training, rats received i.p. injections of the dopamine antagonist haloperidol (HP; 0.1, 0.2 and 0.4 mg/kg). HP produced a dose-related decline in overall response number. In addition, HP dramatically altered the IRT distribution. HP-treated rats showed a dose-related reduction in the proportion of IRTs with low time values (high local rates of responding), and a corresponding increase in the relative number of IRTs with high time values (low local rates of responding). In the second experiment, the neurotoxic agent 6-hydroxydopamine was injected directly into the nucleus accumbens, medial neostriatum or ventrolateral neostriatum in order to determine the effects of DA depletion on lever pressing performance. Dopamine depletion in all regions significantly reduced lever pressing, and dopamine-depleted rats had substantial changes in their IRT distributions. Rats with dopamine depletions showed significant reductions in the proportion of IRTs with low time values, and increases in the relative number of IRTs with high time values. The greatest reductions in response number and the most pronounced alterations of the IRT distribution were shown by rats with ventrolateral neostriatal dopamine depletions.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1993

Different effects of nucleus accumbens and ventrolateral striatal dopamine depletions on instrumental response selection in the rat.

This experiment was undertaken to investigate dopaminergic involvement in food-related instrumental behavior. Rats were tested in an operant chamber in which there was a choice between pressing a lever to receive a preferred food (Bioserve pellets) or feeding upon a less preferred food (lab chow). The lever-pressing schedule was a fixed ratio 5 (FR5). Rats usually pressed the lever at high rates to obtain the preferred food, and typically ate little of the lab chow even though it was freely available in the chamber concurrently with the lever-pressing schedule. The neurotoxic agent 6-hydroxydopamine was injected directly into the nucleus accumbens, medial striatum, or ventrolateral striatum to determine the effects of dopamine depletion on the performance of this task. Depletion of dopamine in the nucleus accumbens led to a dramatic shift in behavior in which there was a significant decrease in lever pressing but a significant increase in consumption of lab chow. The shift away from lever pressing and towards chow consumption in rats with accumbens DA depletions was significantly correlated with a decrease in spontaneous locomotor activity. Dopamine depletions in the medial striatum did not significantly affect lever pressing or chow consumption. Ventrolateral striatal dopamine depletions decreased lever pressing but also tended to reduce consumption of lab chow. Rats with ventrolateral striatal dopamine depletions also showed profound deficits in home-cage feeding, and these rats had to receive wet mash or tube feeding to maintain body weight.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1993

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.

3,4-Dihydroxyphenylacetic Acid↗