Home | | Psychiatry | The Development of Addiction

Chapter: Essentials of Psychiatry: Psychiatric Pathophysiology: Addiction

The Development of Addiction

The Development of Addiction
The acute administration of all addictive drugs, with the pos-sible exception of the benzodiazepines, stimulates dopamine transmission in the projection from the ventral mesencephalon to the nucleus accumbens.

The Development of Addiction

 

The acute administration of all addictive drugs, with the pos-sible exception of the benzodiazepines, stimulates dopamine transmission in the projection from the ventral mesencephalon to the nucleus accumbens. This projection is generally re-ferred to as the mesolimbic dopamine system; Figure 13.1

 


illustrates the capacity of two drugs of abuse – cocaine and ethanol – to increase dopamine transmission in the nucleus accumbens. The pharmacological site of action by which different classes of drugs of abuse activate dopamine trans-mission varies and includes three general cellular mecha-nisms that encompass all drugs of abuse: 1) Receptors for the drug are on dopamine cell bodies and dendrites, and through these receptors drug administration directly stimu-lates dopamine neurons. Nicotine and marijuana are exam-ples of drugs working in part through this mechanism (Cheer et al., 2000; Nisell et al., 1994). 2) Receptors are located prima-rily on GABAergic inhibitory afferents to the dopamine cells, and drug binding to these receptors reduces GABA release, thereby disinhibiting dopamine neuronal activity. Opioids and ethanol produce reward in part by this mechanism (Bunney et al., 2001; Cameron et al., 1997). 3) Finally, drugs can bind to presynaptic receptors to increase the presynaptic release of dopamine without directly altering the activity of dopamine neurons. The primary mechanism in this category is exem-plified by amphetamine-like psychostimulants which bind to the dopamine transporter and increase dopamine release by blocking reuptake and/or promoting the release of dopamine by reverse transport (Seiden et al., 1993).

 

Figure 13.1 also illustrates that mesolimbic dopamine is released by environmental stimuli that are motivationally rel-evant to the organism, regardless of the valence of the stimulus. For example, either positive motivational stimuli such as sex and food, or negative stressful stimuli will increase dopamine release. However, as indicated in Figure 13.1, regardless of the intensity of the natural stimulus, the extent of dopamine release is far less than that produced by drugs. This is especially true for the duration of dopamine release induced by a typical dose of ad-dictive drugs that will endure for many minutes to hours, while a natural stimulus is thought to elevate dopamine for a period of only a few minutes, even if the stimulus itself is present for a greater length of time.

 

Unlike physiological stimuli, the increase in dopamine transmission does not diminish following repeated drug administration (although this varies with drug class, and some tolerance can be demonstrated to all drugs during a binge of drug taking). Thus, repeated drug use is associated with repeated increase in dopamine, thereby providing a repeated stimulus for cellular adaptation. Due to both the relative lack of tolerance to drug-induced dopamine release as well as to the fact that the quantity of release is well in excess of what is seen physiologically with naturally rewarding stimuli (see Figure 13.1), it is thought that dopamine-dependent neuroplastic changes induced by repeated drug use are beyond the physiological range of normal cellular adaptation. This pathological event precipitates a sequence of cellular changes that ultimately produce neuroadaptations that are widespread in cortical and limbic circuitry, and these adaptations constitute the underlying pathophysiology of addiction. Although the addiction-associated neuroadaptations are impacted by drug class, dose and withdrawal period, it is thought that excessive, nonphysiological release of dopamine is a critical initiator of the pathology.

 

Identifying the specific changes in gene expression and cellular function that are associated with the development of ad-diction is an area of active research, and the interested reader is referred to recent reviews of this literature (Nestler, 2001; Kalivas, 2002).

Study Material, Lecturing Notes, Assignment, Reference, Wiki description explanation, brief detail
Essentials of Psychiatry: Psychiatric Pathophysiology: Addiction : The Development of Addiction |


Privacy Policy, Terms and Conditions, DMCA Policy and Compliant

Copyright © 2018-2024 BrainKart.com; All Rights Reserved. Developed by Therithal info, Chennai.