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

Neurocircuitry of Addiction

The theory is advanced that the common denominator of a wide range of addictive substances is their ability to cause psychomotor activation. This view is related to the theory that all positive reinforcers activate a common biological mechanism associated with approach behaviors and that this mechanism has as one of its components dopaminergic fibers that project up the medial forebrain bundle from the midbrain to limbic and cortical regions. Evidence is reviewed that links both the reinforcing and locomotor-stimulating effects of both the psychomotor stimulants and the opiates to this brain mechanism. It is suggested that nicotine, caffeine, barbiturates, alcohol, benzodiazepines, cannabis, and phencyclidine----each ofwhich also has psychomotor stimulant actions--may activate the docaminergic fibers or their output circuitry. The role of physical dependence in addiction is suggested to vary from drug to drug and to be of secondary importance in the understanding of compulsive drug self-administration. Attempts at a general theory of addiction are attempts to isr late--from a variety of irrelevant actionsmthose drug actions that are responsible for habitual, compulsive, nonmedical drug self-administration. The common assumption of addiction theorists is that general principles of addiction can be learned from the study of one drug and that these principles will have heuristic value for the study of other drugs. Thus far, attempts at a general theory of addiction have failed to isolate common actions that can account for addiction across the range of major drug classes. A major stumbling block has been the psychomotor stimulants--amph etamine and cocainemwhich do not readily fit models traditionally based on depressant drug classes. The present article offers a new attempt at a general theory of addiction. It differs from earlier theories (e.g., Collier, 1968; Himmelsbach, 1943; Jaffe & Sharpless, 1968; Jellinek, 1960; Kalant, 1977; Lindsmith, 1947; Solomon & Corbit, 1974) in that it is based on the common denominator of the psychomotor stimulants---amphetamine, cocaine, and related drugs---rather than on the common denominator of the socalled depressant drugs~opiates, barbiturates, alcohol, and others. We take up two topics before presenting the new theory. First, we briefly discuss the heuristic value of a biological approach and suggest that the biologist's distinction between homology and analogy offers a useful insight. Next we discuss the shortcomings of earlier theories--variants of dependence theory. Then we outline the new theory and review the relevant evidence for its three major assertions: (a) that all addictive drugs have psychomotor stimulant actions, (b) that the stimulant actions of these different drugs have a shared biological mechanism, and (c) that the biological mechanism of these stimulant

A psychomotor stimulant theory of addiction

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

The principal features and mechanisms of dopamine modulation in the prefrontal cortex

Firing properties of substantia nigra dopaminergic neurons in freely moving rats

The effects of phencyclidine and N-allylnormetazocine on midbrain dopamine neuronal activity

Activity of A9 and A10 dopaminergic neurons in unrestrained rats: further characterization and effects of apomorphine and cholecystokinin.

Mesolimbic and mesocortical dopamine activation induced by phencyclidine: contrasting pattern to striatal response

Single-unit electrophysiological recording techniques were used to sample the basal activity of antidromically identified nigrostriatal and mesoaccumbens dopamine (NSDA and MADA, respectively) neurons and to examine the responsiveness of these cells to dopamine agonist-induced inhibition of cell firing rate in either chloral hydrate-anesthetized or paralyzed rats. Paralyzed rats exhibited a greater percentage of burst-firing cells (69%) than did anesthetized animals (37%). Furthermore, paralyzed rats were less sensitive to the mixed D1/D2 DA receptor agonist apomorphine and the selective D2 DA receptor agonist quinpirole. However, significantly higher doses of d-amphetamine were required in paralyzed animals only with respect to inhibiting MADA neurons. The abilities of apomorphine and quinpirole to inhibit NSDA cell firing were rate-dependent in both anesthetized and paralyzed rats, whereas d-amphetamine-induced inhibition was rate dependent only in anesthetized animals. In contrast, apomorphine- and quinpirole-induced inhibition of MADA neurons were rate-dependent only in anesthetized rats, whereas d-amphetamine-induced inhibition was rate-dependent only in paralyzed animals. These results suggest that general anesthesia exerts subtle effects on the basal activity and pharmacological responsiveness of midbrain dopamine neurons.

Arthur S. Freeman

Papers

Firing properties of substantia nigra dopaminergic neurons in freely moving rats

The effects of phencyclidine and N-allylnormetazocine on midbrain dopamine neuronal activity

Activity of A9 and A10 dopaminergic neurons in unrestrained rats: further characterization and effects of apomorphine and cholecystokinin.

Mesolimbic and mesocortical dopamine activation induced by phencyclidine: contrasting pattern to striatal response

Chloral hydrate anesthesia alters the responsiveness of identified midbrain dopamine neurons to dopamine agonist administration.