And L Judson Chandler PhD

Alcohol is a major drug of use and abuse in the United States. An estimated 15 million Americans (1988 NHIS study) are alcohol abusers or alcohol dependent. Lifetime prevalence of alcohol dependence is estimated at 13 and 4 for American men and women over 18 yr of age, respectively (1). It is well established that chronic excessive ethanol consumption produces marked deficits in cognitive and motor abilities (2,3). Alcohol is a leading cause of adult dementia in the United States, accounting...

Howard C Becker PhD and Nicole Redmond PhD

It is well known that continued excessive alcohol consumption can lead to the development of physiological dependence. When drinking is abruptly terminated or substantially reduced in the dependent individual, a characteristic withdrawal syndrome ensues. As with other central nervous system (CNS) depressants, withdrawal symptoms associated with cessation of chronic alcohol use are opposite in nature to the effects of intoxication. Thus, clinical features of alcohol withdrawal include signs of...

Summary And Conclusions

Human and animal studies have clearly established that chronic alcohol intake causes a loss of brain mass as a result of ethanol-induced brain damage. Although human studies show loss of brain tissue and the loss of specific brain nuclei after years of alcohol consumption, recent animal studies have indicated that neuronal loss can occur after only a few days of binge drinking. The neuropathol-ogy in humans involves both gray and white matter, whereas the animal studies have focused on neuronal...

W Zieglgansberger G Rammes R Spanagel W Danysz and Ch Parsons

The taurine analog acamprosate (calcium acetylhomotaurinate) has received considerable attention in Europe for its ability to prevent relapse in abstained alcoholics (1) Chapter 28 and has been suggested to act by reducing craving associated with conditioned withdrawal (2,3). 2. ANTICRAVING AND ANTIRELAPSE PROPERTIES OF ACAMPROSATE Novel aspects of addictive behavior to alcohol (craving, relapse, and sensitization processes) are uncovered by a new animal model of long-term, free-choice, alcohol...

Drugs Of Abuse Influence Synaptic Plasticity In The Nucleus Accumbens

The NAc occupies a key position in the neurocircuitry of motivation and reward and is the site of many persistent changes associated with chronic drug exposure (96). Neurons in the NAc consist of medium spiny GABA neurons (90 ) and several populations of interneurons (10 ). The medium spiny neurons are the output neurons of the NAc and receive convergent DA and glutamate inputs. The interneurons play important roles in information processing within the NAc and may also be regulated by DA and...

Glutamate And Dopamine Interactions In The Motive Circuit

Glutamate and Dopamine Receptors Extracellular dopamine binds to two major families of receptors D1-like, which consists of D1 and D5 receptors, and D2-like, which consists of D2, D3, and D4 receptors. The receptor subtypes within each group share molecular and pharmacological properties but can differ in their anatomical distribution. The D1 receptor family is coupled to G proteins and is associated with the activation of adenylyl cyclase. In contrast, the family of D2 receptors are...

Robert W Peoples PhD

Alcohol is arguably the oldest drug known to man, its use dating back at least 10,000 yr to the dawn of human civilization (1). Although illicit drug use often receives more attention in contemporary society, alcohol abuse exacts a devastating toll In the United States at present, over 7 of the population meet diagnostic criteria for alcohol abuse or alcoholism (2), over 28 of children under 18 yr of age are exposed to alcohol abuse or dependence in the home (3), and the overall economic cost...

Mechanisms Of Methamphetamine Toxicity

As discussed above, increases in the extracellular concentrations of both DA and glutamate within the striatum appear to contribute to MA-induced damage to dopaminergic nerve terminals. Many of the manipulations used to identify the role of DA in mediating MA-induced damage also modify MA-induced changes in the extracellular concentrations of glutamate. These findings suggest that the release of both DA and glutamate are obligatory in the MA toxicity cascade (9,10,33,34). For example, D2...

The Role Of Glutamate Receptor Subtypes In Opiate Withdrawal

Glutamate receptors have been divided into two broad categories iontotropic and metabotropic. Iontotropic glutamate receptors contain cation-specific ion channels as a component of their protein complex, whereas metabotropic glutamate receptors are coupled to G-proteins and modulate intracel-lular second-messenger systems. Iontotropic receptors are divided into three main subtypes N-methyl-d-aspartate (NMDA), acid (AMPA), and kainate. Eight different clones for metabotropic glutamate (mGlu)...

AMPA Receptors

AMPA receptor antagonists may modulate AMPA receptor function by acting at the glutamate recognition site competitive antagonists or at a distinct allosteric regulatory site for 2,3-benzodi-azepines negative allosteric modulators . In addition, CA2 -permeable AMPA receptors can be antagonized by a diverse group of cationic channel blockers, including polyamines, spider and wasp toxins such as Joro spider toxin JSTX , and IEM-1460. Recent and detailed reviews of AMPA-receptor structure,...