Dependence opiate receptor

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]. 

Increasing evidence indicates that a chronic opiate-induced upregulation of the cAMP pathway, manifested by increased concentrations of adenylyl cyclase, PKA and several phosphoprotein substrates for the protein kinase, contributes to opiate tolerance, dependence and withdrawal exhibited by locus ceruleus neurons [66]. This upregulated cAMP pathway can be viewed as a homeostatic response of the neurons to persistent opiate inhibition of the cells. In the chronic opiate-treated state, the upregulated cAMP pathway helps return neuronal firing rates to control levels, i.e. tolerance. Upon abrupt removal of the opiate via the administration of an opiate receptor antagonist, the upregulated cAMP accounts for part of the withdrawal activation of the cells. 

Alkaloids such as boldine, codeine, narceine and morphine are active factors in their receptors. Boldine has morphine-like properties and is active on opioid receptors. It may be used to treat stomach disorders and as metabolic stimulant. As it is similar to morphine, boldine can also be considered in the possible development of treatments for narcotic dependence. Codeine also binds to opiate receptors, and specifically functions to reduce bronchial secretions. Codeine can also be used as a cough suppressant when acting on the centre of the medulla oblongata and as a sedative agent. 

Postmortem studies of humans with opiate dependence have shown that p-opiate receptor density is unchanged in frontal cortex, thalamus, and caudate. In contrast, a-2 adrenoceptor density is decreased in these... 

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. 

D-Ala-deltorphin-II induces 6-opiate receptor mediated analgesia in frogs [55] and also in the invertebrate land snail (Cepaea nemoralis) [56]. When administered by intrathecal injection in rats, D-Ala-deltorphin-II produces a dose-related inhibition of the tail-flick response (threshold 0.6 nmol/rat). Its inhibitory effect lasts 10 60 min, depending on the dose, and is naltrindole reversible [57]. Wang et al. [25] demonstrated that D-Ala-deltorphin-II inhibited A6 and C fiber evoked responses from nociceptive neurons in the superficial and deeper dorsal horn of the rat medulla. 

Fig. 13.3. Schematic representation of proton transfer between an acceptor base of the opiate receptor and a protonated morphinan. Position of equilibrium strongly dependent on relative basicities of acceptor and donor.

Previous work, which has not been revisited, showed that sulfatides are necessary for the optimal function of enzymes such as sodium-potassium-dependent ATPase, and the sulfatide content seems to be directly related to the activity of the enzyme (Karlsson et al., 1974). Sulfatides may also be involved in the functioning of certain opiate receptors (Craves et al., 1980) and in chloride transport systems (Zalc et al., 1978). Implantation in the spinal cord of a hybridoma secreting specific antisulfatide antibodies has been shown to cause demyelination of the CNS in the rat (Rosenbluth et al., 2003). Antisulfatide antibodies have been found in HIV... 

Kosterlitz HW, Hughes J (1977) Opiate receptors and endogenous opioid peptides in tolerance and dependence. Adv Exp Med Biol 85 141-154. 

Heroin was first synthesized from morphine over a century ago. Since then, it has become one of the most abused substances. Research into why it produces such powerful effects has led to the discovery of specific opiate receptors and endogenous opioids (enkephalins and endorphins). These peptides appear to be neurotransmitters involved with the sensation of pain and pleasure. A number of opiates and synthetic opioids are available and can lead to dependency, including morphine, heroin, propoxyphene (Darvon), methadone, meperidine (Demerol), pentazocine (Talwin), hy-dromorphone (Dilaudid), oxycodone (Percodan), and hydrocodone (Vicodin, Damason-P), and codeine. 

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