Dopamine transmission in the initiation and expression of drug- and stress-induced sensitization of motor activity

Phasic versus tonic dopamine release and the modulation of dopamine system responsivity: a hypothesis for the etiology of schizophrenia

Many lesion studies report an amazing variety of deficits in behavioral functions that cannot possibly be encoded in great detail by the relatively small number of midbrain dopamine neurons. Although hoping to unravel a single dopamine function underlying these phenomena, electrophysiological and neurochemical studies still give a confusing, mutually exclusive, and partly contradictory account of dopamine's role in behavior. However, the speed of observed phasic dopamine changes varies several thousand fold, which offers a means to differentiate the behavioral relationships according to their time courses. Thus dopamine is involved in mediating the reactivity of the organism to the environment at different time scales, from fast impulse responses related to reward via slower changes with uncertainty, punishment, and possibly movement to the tonic enabling of postsynaptic motor, cognitive, and motivational systems deficient in Parkinson's disease.

Multiple Dopamine Functions at Different Time Courses

A model is proposed for integrating the neural and cognitive aspects of the positive symptoms of acute schizophrenia, using evidence from postmortem neuropathology and neurochemistry, clinical and preclinical studies of dopaminergic neurotransmission, anatomical connections between the limbic system and basal ganglia, attentional and other cognitive abnormalities underlying the positive symptoms of schizophrenia, specific animal models of some of these abnormalities, and previous attempts to model the cognitive functions of the septohippocampal system and the motor functions of the basal ganglia Anatomically, the model emphasises the projections from the septohippocampal system, via the subiculum, and the amygdala to nucleus accumbens, and their interaction with the ascending dopaminergic projection to the accumbens Psychologically, the model emphasises a failure in acute schizophrenia to integrate stored memories of past regularities of perceptual input with ongoing motor programs in the control of current perception A number of recent experiments that offer support for the model are briefly described, including anatomical studies of limbic-striatal connections, studies in the rat of the effects of damage to these connections, and of the effects of amphetamine and neuroleptics, on the partial reinforcement extinction effect, latent inhibition and the Kamin blocking effect; and studies of the latter two phenomena in acute and chronic schizophrenics

The neuropsychology of schizophrenia.

Rationale Dopamine neurotransmission has long been known to exert a powerful influence over the vigor, strength, or rate of responding. However, there exists no clear understanding of the computational foundation for this effect; predominant accounts of dopamine’s computational function focus on a role for phasic dopamine in controlling the discrete selection between different actions and have nothing to say about response vigor or indeed the freeoperant tasks in which it is typically measured. Objectives We seek to accommodate free-operant behavioral tasks within the realm of models of optimal control and thereby capture how dopaminergic and motivational manipulations affect response vigor. Methods We construct an average reward reinforcement learning model in which subjects choose both which action to perform and also the latency with which to perform it. Optimal control balances the costs of acting quickly against the benefits of getting reward earlier and thereby chooses a best response latency. Results In this framework, the long-run average rate of reward plays a key role as an opportunity cost and mediates motivational influences on rates and vigor of responding. We review evidence suggesting that the average reward rate is reported by tonic levels of dopamine putatively in the nucleus accumbens. Conclusions Our extension of reinforcement learning models to free-operant tasks unites psychologically and computationally inspired ideas about the role of tonic dopamine in striatum, explaining from a normative point of view why higher levels of dopamine might be associated with more vigorous responding.

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Tonic dopamine: opportunity costs and the control of response vigor.

The N-methyl-D-aspartate (NMDA) receptor-mediated regulation of the release of newly synthesized [3H]dopamine [( 3H]DA) was studied in vitro, both on rat striatal slices using a new microsuperfusion device and on rat striatal synaptosomes. Under Mg2(+)-free medium conditions, the NMDA (5 X 10(-5) M)-evoked release of [3H]DA from slices was found to be partly insensitive to tetrodotoxin (TTX). This TTX-resistant stimulatory effect of NMDA was blocked by either Mg2+ (10(-3) M) or the noncompetitive antagonist MK-801 (10(-6) M). In addition, the TTX-resistant NMDA-evoked response could be potentiated by glycine (10(-6) M) in the presence of strychnine (10(-6) M). The coapplication of NMDA (5 X 10(-5) M) and glycine (10(-6) M) stimulated the release of [3H]DA from striatal synaptosomes. This effect was blocked by Mg2+ (10(-3) M) or MK-801 (10(-5) M). These results indicate that some of the NMDA receptors involved in the facilitation of DA release are located on DA nerve terminals. These presynaptic receptors exhibit pharmacological properties similar to those described in electrophysiological studies for postsynaptic NMDA receptors.

Glutamatergic control of dopamine release in the rat striatum: evidence for presynaptic N-methyl-D-aspartate receptors on dopaminergic nerve terminals.

In vivo presynaptic control of dopamine release in the cat caudate nucleus--II. Facilitatory or inhibitory influence of L-glutamate.

L-glutamate-evoked release of dopamine from synaptosomes of the rat striatum: involvement of AMPA and N-methyl-D-aspartate receptors.

Riluzole inhibits the release of glutamate in the caudate nucleus of the cat in vivo

In vivo presynaptic control of dopamine release in the cat caudate nucleus--III. Further evidence for the implication of corticostriatal glutamatergic neurons.

G. Godeheu

Papers

Glutamatergic control of dopamine release in the rat striatum: evidence for presynaptic N-methyl-D-aspartate receptors on dopaminergic nerve terminals.

In vivo presynaptic control of dopamine release in the cat caudate nucleus--II. Facilitatory or inhibitory influence of L-glutamate.

L-glutamate-evoked release of dopamine from synaptosomes of the rat striatum: involvement of AMPA and N-methyl-D-aspartate receptors.

Riluzole inhibits the release of glutamate in the caudate nucleus of the cat in vivo

In vivo presynaptic control of dopamine release in the cat caudate nucleus--III. Further evidence for the implication of corticostriatal glutamatergic neurons.