The capacity to predict future events permits a creature to detect, model, and manipulate the causal structure of its interactions with its environment. Behavioral experiments suggest that learning is driven by changes in the expectations about future salient events such as rewards and punishments. Physiological work has recently complemented these studies by identifying dopaminergic neurons in the primate whose fluctuating output apparently signals changes or errors in the predictions of future salient and rewarding events. Taken together, these findings can be understood through quantitative theories of adaptive optimizing control.

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A Neural Substrate of Prediction and Reward

http://umh1946.edu.umh.es/wp-content/uploads/sites/172/2015/04/Neurocircuitry-of-addiction1.pdf

Neurocircuitry of Addiction

Schultz, Wolfram. Predictive reward signal of dopamine neurons. J. Neurophysiol. 80: 1–27, 1998. The effects of lesions, receptor blocking, electrical self-stimulation, and drugs of abuse suggest t...

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Predictive Reward Signal of Dopamine Neurons

https://lsa.umich.edu/psych/research&labs/berridge/publications/Berridge&RobinsonBrResRev1998.pdf

What is the role of dopamine in reward: hedonic impact, reward learning, or incentive salience?

Pharmacological and biochemical criteria can be used to separate those dopamine receptors which are linked to the enzyme adenylyl cyclase and those which are not.

Multiple receptors for dopamine.

Erratum to “the role of dopamine in drug abuse viewed from the perspective of its role in motivation”

Conditioned saccharin avoidance and sensitization to drugs of abuse.

Ipsiversive-cataleptogenic Neurons of Nigra pars Reticulata: Out-put Pathways of Striatal Dopaminergic Responses

Loren (Larry) H. Parsons passed away at the age of 51. In spite of his premature departure, Larry much contributed to the drug abuse field. Since his graduate studies for the Ph.D. in Chemistry in J.B. Justice lab, microdialysis is the tread that links Larry's research topics, namely, the role of dopamine (DA), serotonin (5-HT), gamma-aminobutyric acid (GABA), glutamate and endocannabinoids (eCBs) in drug reinforcement and dependence. Larry was the first to show that abstinence from chronic cocaine reduces extracellular DA in the NAc, consistent with the so called 'dopamine depletion hypothesis' of cocaine addiction. Another Larry's major contributions are the studies on 5-HT and 5-HT receptors' role in cocaine stimulant actions, which resulted in the identification of 5-HT1B receptors as a critical substrate of cocaine reinforcement. By applying mass spectrometry to eCBs analysis in brain dialysates, Larry's lab showed that ethanol, heroin, nicotine and cocaine differentially affect anandamide and 2-arachidonoylglicerol overflow in the NAc shell, a critical site of drugs of abuse DA stimulant actions. Larry also applied microdialysis to study GABA and glutamate's role in ethanol dependence and heroin reinforcement, providing in vivo evidence for a sensitization of corticotropin-releasing factor-dependent release of GABA in the central amygdala in withdrawal from chronic ethanol and for a reduction of GABA transmission in the ventral pallidum in heroin but not cocaine intravenous self-administration. Larry showed the wide possibilities of microdialysis as a general purpose methodology for monitoring neurotransmitters and neuromodulators in the brain extracellular compartment. From this viewpoint, he stands as the best advocate for microdialysis.

Loren Parsons' contribution to addiction neurobiology

Drugs acting on muscarinic cholinergic receptors, dopaminergic D-1, D-2, D-3, D-4 receptors and glutamatergic N-Methyl-D-Aspartate (NMDA) receptors are known to exert major influences on motor functions by an action on the Basal Ganglia. This strikingly contrasts with the elusiveness of the influences of these receptors on the function of striatal neurons as measured by electrophysiological methods that readily demonstrate the action of classical neurotransmitter receptors such as those of the glutamate/AMPA or GABA-A type. For example, only in recent times, almost 30 years after the appraisal of dopamine (DA) deficiency as a causal factor in Parkinson’s disease, the electrophysiological actions of DA at the single cell level are starting to be unraveled (Calabresi et al., 1987; Lacey et al, 1987; Kitai and Surmeier, 1993). The reason for the elusive nature of dopaminergic, muscarinic and NMDA transmission might be the fact that they do not directly trigger or inhibit action potentials but rather gate or modulate their generation by “fast” neurotransmitter receptors.

Gaetano Di Chiara

Papers

Erratum to “the role of dopamine in drug abuse viewed from the perspective of its role in motivation”

Conditioned saccharin avoidance and sensitization to drugs of abuse.

Ipsiversive-cataleptogenic Neurons of Nigra pars Reticulata: Out-put Pathways of Striatal Dopaminergic Responses

Loren Parsons' contribution to addiction neurobiology

Acetylcholine, Dopamine and NMDA Transmission in the Caudate-Putamen: Their Interaction and Function as a Striatal Modulatory System