Opiates dependence mechanisms

It is no coincidence that many of the artists who combine a Poe-like reflection on technologies of communication as worldmaking devices with the presentation of science fictional scenarios frequently make use of mind altering substances as plot devices, and otherwise, as Poe notoriously also did. A drug, hke other of Poe s mechanisms of displacement, is a medium that alters perceptions and shifts the parameters of the user s world. Perhaps because of the reports of alcoholism and opiate dependency that surround Poe, he has been a crypto-reference for various strands of experimental popular music from the 1960s onward. While Byron seems to be the main prototype for Jimi Hendrix s flamboyant persona and Georgian ruffles, his frequent journeys to outer space ( EXP, Third Stone from the Sun ), identification with aliens, and excursions undersea and to the poles ( 1983 A Merman... 

Upregulation of the cyclic AMP pathway is one mechanism underlying opiate addiction. The mechanisms by which opiates induce tolerance, dependence and withdrawal in specific target neurons has been a major focus of research for many years. The inability to account for prominent aspects of opiate addiction solely on the basis of alterations in endogenous opioid peptides or in opiate receptors has shifted attention to postreceptor mechanisms [66]. 

Upregulation of the cAMP pathway may be a common mechanism by which a number of neuronal cell types respond to chronic opiates and develop tolerance and dependence (see Ch. 56). There is also evidence that similar mechanisms involving alterations in the cAMP second-messenger and protein phosphorylation pathway may mediate aspects of addiction to other types of drugs of abuse, for example, cocaine and alcohol [66],... 

In the early days of opiate use, abuse, and intoxication and prior to completion of the neuroadaptive mechanisms, that mediate opiate receptor desensitization, opiate intoxication alternates with normal functioning. Later, after the opiate receptors adapt and dependency is established, the abuser may experience very little euphoria, but mostly withdrawal-free periods alternating with withdrawal. 

Cross-tolerance occurs between all opiates that act primarily via the mu receptors. This is the basis of the methadone substitution therapy which is commonly used to withdraw people who are dependent on heroin or morphine methadone is used because of its relatively long half-life (about 12 hours) and its ease of administration in an oral form. Cross-tolerance does not occur between the opiates and other classes of dependence-producing drugs such as the barbiturates, alcohol or the amphetamines, which act through different mechanisms. 

Early theories, by referring to opiate addiction as a model, placed major emphasis on physical dependence as a factor of drug addiction (Himmelsbach, 1943). More recent formulations, apart from providing a theory for the mechanism of tolerance and dependence (opponent process theory) (Solomon, 1977), have moved the emphasis from... 

Following along these lines Yamamoto e al. (89) examined the effects of chronic morphine treatment on the Mg -dependent ATPase of synaptic vesicles. Since this enzyme has been implicated in the regulation of neurotransmitter release (90,91), it appears a likely enzyme candidate to be altered by opiates. Consistent with this anticipation, it was found that the activity of Mg dependent ATPase in mouse brain synaptic vesicles was significantly increased with tolerance development while that of the Mg 2+ dependent ATPase and Na+, K" activated ATPase from SPM fractions were not altered. Kendrick t al. (92) have shown that Mg +-ATPase may be involved in the accumulation of Ca + by synaptic vesicles the increased Ca2+ content of vesicles seen in tolerant animals could thus arise from increased enzymatic activity. Such a homeostatic mechanism would serve to overcome reduced levels of neurotransmitter release due to the opiate. 

Lobeline has been reported as a useful agent to treat dependency on drugs such as cocaine, amphetamine, caffeine, pheny Icy dine, opiates, barbiturates, benzodiazepines, cannabinoids, hallucinogens, alcohol, and, especially, nicotine. Dwoskin [55] described a novel mechanism of action and potential use for lobeline as a treatment for psychostimulant abuse. 

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