The Role of Dopamine in Locomotor Activity and Learning

Hippocampal connections and spatial discrimination.

Motivational views of reinforcement: implications for understanding the behavioral functions of nucleus accumbens dopamine.

The unilateral 6-hydroxydopamine lesion model in behavioral brain research. Analysis of functional deficits, recovery and treatments.

Although the Skinnerian ‘Empirical Law of Effect’ does not directly consider the fundamental properties of stimuli that enable them to act as reinforcers, such considerations are critical for determining if nucleus accumbens dopamine systems mediate reinforcement processes. Researchers who have attempted to identify the critical characteristics of reinforcing stimuli or activities have generally arrived at an emphasis upon motivational factors. A thorough review of the behavioral literature indicates that, across several different investigators offering a multitude of theoretical approaches, motivation is seen by many as being fundamental to the process of reinforcement. The reinforcer has been described as a goal, a commodity, an incentive, or a stimulus that is being approached, self-administered, attained or preserved. Reinforcers also have been described as activities that are preferred, deprived or in some way being regulated. It is evident that this ‘motivational’ or ‘regulatory’ view of reinforcement has had enormous influence over the hypothesis that DA directly mediates ‘reward’ or ‘reinforcement’ processes. Indeed, proponents of the DA/reward hypothesis regularly cite motivational theorists and employ their language. Nevertheless, considerable evidence indicates that low/moderate doses of DA antagonists, and depletions of DA in nucleus accumbens, can suppress instrumental responding for food while, at the same time, these conditions leave fundamental aspects of reinforcement (i.e. primary or unconditioned reinforcement; primary motivation or primary incentive properties of natural reinforcers) intact. Several complex features of the literature on dopaminergic involvement in reinforcement are examined below, and it is argued that the assertions that DA mediates ‘reward’ or ‘reinforcement’ are inaccurate and grossly oversimplified. Thus, it appears as though it is no longer tenable to assert that drugs of abuse are simply turning on the brain’s natural ‘reward system’. In relation to the hypothesis that DA systems are involved in ‘wanting’, but not ‘liking’, it is suggested in the present review that ‘wanting’ has both directional aspects (e.g. appetite to consume food) and activational aspects (e.g. activation for initiating and sustaining instrumental actions; tendency to work for food). The present paper reviews findings in support of the hypothesis that low doses of DA antagonists and accumbens DA depletions do not impair appetite to consume food, but do impair activational aspects of motivation. This suggestion is consistent with the studies showing that low doses of DA antagonists and accumbens DA depletions alter the relative allocation of instrumental responses, making the animals less likely to engage in instrumental responses that have a high degree of work-related response costs. In addition, this observation is consistent with studies demonstrating that accumbens DA depletions make rats highly sensitive to ratio requirements on operant schedules. Although accumbens DA is not seen as directly mediating appetite to consume food, principles of behavioral economics indicate that accumbens DA could be involved in the elasticity of demand for food in terms of the tendency to pay work-related response costs. Future research must focus upon how specific aspects of task requirements (i.e. ratio requirements, intermittence of reinforcement, temporal features of response requirements, dependence upon conditioned stimuli) interact with the effects of accumbens DA depletions, and which particular factors determine sensitivity to the effects of DA antagonism or depletion. # 2002 Elsevier Science B.V. All rights reserved.

Research report Motivational views of reinforcement: implications for understanding the behavioral functions of nucleus accumbens dopamine

Relationships between indices of behavioral asymmetries and neurochemical changes following mesencephalic 6-hydroxydopamine injections.

A further localization of inhibitory deficits resulting from septal ablation

Selective forebrain depletions of either norepinephrine or serotonin were produced in separate groups of rats by placement of lesions in the brainstem noradrenergic area and in the dorsal and median raphe´nuclei respectively. Rats with norepinephrine depleting lesions exhibited an attenuation relative to intact animals of both the anorexic and locomotor stimulatory effects of amphetamine. In contrast, depletion of serotonin by the raphe´lesion enhanced the locomotor stimulation induced by amphetamine but did not affect the anorexic efficacy of amphetamine. Neither brain lesion, however, reliably altered the animal's response to either the anorexic or activity effects of fenfluramine.

Effects of selective forebrain depletions of norepinephrine and serotonin on the activity and food intake effects of amphetamine and fenfluramine.

A comparison of the effects in rats of four dose levels of d- and 1-amphetamine (0.5, 1.0, 2.0 and 4.0 mg/kg) on development of a taste aversion to a 0.1% saccharin solution showed that d-amphetamine was approximately 4 times as potent as 1-amphetamine in inducing a taste aversion to saccharin. The aversion was obtained in both forced- and free-choice tests. A 2–4 fold differential in efficacy was found when the same dose levels of both amphetamine isomers were tested for their effects in reducing water intake. The approximately 4-fold greater effectiveness of the d-isomer suggested that the taste aversion may be mediated by a dopaminergic system. In addition, it was suggested that the taste aversion behavior represented a conditioned anorexic effect rather than being indicative of a noxious or aversive consequence of the amphetamine.

Amphetamine-induced taste aversion: A comparison of d- versus 1-amphetamine

In rats repeated 2 mg/kg injections of d -amphetamine given 30 min after imbibition of a 0.1% saccharin solution proved to be as effective in reducing saccharin intake as 2 mg/kg injections of d -amphetamine given 30 min before presentation of this saccharin solution. Treatment with alpha-methyl-para-tyrosine blocked the effect on saccharin intake of amphetamine given before, but not amphetamine given after presentation of the saccharin. After amphetamine injections were terminated, subsequent saccharin vs. water preference testing showed that the amphetamine injections given after but not the injections given before resulted in a long-term aversion to the saccharin solution. In a second experiment, the 2 mg/kg dose of amphetamine was shown to facilitate intracranial self-stimulation as well as to induce an aversion to saccharin.

Robert J. Carey

Papers

Relationships between indices of behavioral asymmetries and neurochemical changes following mesencephalic 6-hydroxydopamine injections.

A further localization of inhibitory deficits resulting from septal ablation

Effects of selective forebrain depletions of norepinephrine and serotonin on the activity and food intake effects of amphetamine and fenfluramine.

Amphetamine-induced taste aversion: A comparison of d- versus 1-amphetamine

Long-term aversion to a saccharin solution induced by repeated amphetamine injections.