Withdrawal, drug, animal models

It is beheved that phenomena such as sensitization, tolerance and drug-dependence might also involve synaptic plasticity. In fact, numerous studies indicate that NMDA receptor antagonists block sensitization to amphetamine and cocaine as well as tolerance and dependence to ethanol and opioids in animal models (Trujillo and Akil 1991 Pasternak and Inturrisi 1995 Trujillo and Akil 1995 Mao 1999). Recent studies indicate that the uncompetitive NMDA receptor antagonists dextromethorphan, memantine and neramexane not only prevent the development of morphine tolerance, but also reverse estabhshed tolerance in the continuing presence of this opioid, prevent the expression of withdrawal symptoms in rats (Popik and Skolnick 1996 Popik and Danysz 1997 Popik and Kozela 1999 Houghton et al. 2001) and attenuate the expres-... 

Emmett-Oglesby MW, Mathis DA, Moon RTY, Lai H (1990) Animal models of drug withdrawal symptoms. Psychopharmacology 707 292—309. 

LSD produces a rapid and complete tolerance, but it is not powerfully reinforcing the way drugs of abuse like cocaine and heroin are. LSD does not produce any known withdrawal syndrome (Abraham et al. 1996). It does not produce positive reinforcement in animal self-administration models. Concurrently in humans, it does not lead to patterns of repeti-... 

CSA administration causes acute changes in renal hemodynamics and function in patients and in healthy human volunteers [17]. The phenomenon is reversible with drug dosage decrease or withdrawal. These changes were also demonstrated after different doses and route of administration in animals and indeed, acute CSA-induced nephrotoxicity models are consistent. Renal structural abnormalities seem in experimental studies or in patients biopsies are minimal to absent and non-specific, even when renal dysfunction is severe [15,18]. 

Caffeine has been proposed as a model of drug abuse despite the facts that its sale is largely unrestricted and that heavy consumption of caffeine-containing beverages is not considered to be drug abuse. A recent exhaustive review of caffeine dependence focused on the potential for abuse of caffeine and the nature of tolerance and withdrawal and presents a symposium of current knowledge as to the site(s) and mechanism of action of caffeine. A second comprehensive review of human and animal data on coffee and caffeine consumption and caffeine dependence, withdrawal, and reinforcement also has been published. " The information below represents a broad overview of these topics, and the reader interested in more detail is urged to consult these two reviews. " ... 

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