Reinforcement opiates

The reinforcing effects of opiate drugs involve a number of neuronal pathways [21]. In the VTA, opiates stimulate p-opioid receptors on GABA neurons that synapse on dopamine neurons. This inhibits the GABA neurons, leading to disinhibition of the dopamine neurons and enhanced dopamine release in the nucleus accumbens and other target areas (Fig. 56-3). Opiates also exert dopamine-independent effects in the nucleus accumbens by activating... 

Stewart J (1983) Conditioned and unconditioned drug effects in relapse to opiate and stimulant drug-administration. Prog Neuropsychopharmacol Biol Psychiatry 7 591-597 Stolerman IP (1988) Characterization of central nicotinic receptors by studies on the nicotine cue and conditioned taste aversion in rats. Pharmacol Biochem Behav 30 235-242 Stolerman IP (1989) Discriminative stimulus effects of nicotine in rats trained under different schedules of reinforcement. Psychopharmacology 97 131-138 Stolerman IP (1999) Inter-species consistency in the behavioural pharmacology of nicotine dependence. Behav Pharmacol 10 559-580... 

There are two main hypotheses about the involvement of endogenous opioid systems in the maintenance of self-injurious behaviors (Sandman, 1988 Buitelaar, 1993). The pain hypothesis suggests that in some subjects self-injury does not induce pain because excessive basal activity of opioid systems in the CNS has led to an opioid analgesic state. The addiction hypothesis posits that particularly repetitive and stereotyped forms of self-injury stimulate the production and release of en-dogeneous opioids. Therefore, chronic maintenance of self-injury may be due to addiction to endogenous opioids or to positive reinforcement by a central release of opioids triggered by the self-injurious behavior. Irrespective of which hypothesis one favors, treatment with opiate antagonists seems to be a rational approach. 

Curran C, Byrappa N McBride A (2004). Stimulant psychosis systematic review. British Journal of Psychiatry, 185, 196-204 Dallery J, Silverman K, Chutuape MA, Bigelow GE Stitzer ML (2001). Voucher-based reinforcement of opiate plus cocaine abstinence in treatment-resistant methadone patients effects of reinforcer magnitude. Experimental and Clinical Psychopharmacology, 9, 317-25... 

Portenoy and Payne (1997) observe that physical dependency as a result of prolonged use of opiates in programs of pain management does not reliably lead to addiction. "A reasonable hypothesis is that addiction results from the interaction between the reinforcing properties of opioid drugs and any number of characteristics... specific to the individual... such as the capacity for euphoria from an opioid and psychopathy" (582). 

Met-enkephalinamide, an endogenous delta selective opiate, is shown to modulate TCR/CD3-induced fluctuations in free intracellular calcium levels in human T lymphocytes, reinforcing the hypothesis of a direct immunomod-ulation by endogenous opioids [35]. Deltorphin and [D-Ala2,D-Leu5]enkeph-alin (DADLE) induced increases in intracellular calcium [Ca2+] were... 

These natural reward centers have developed over the course of evolution to reinforce useful behaviors (e.g., pleasure, sexual satisfaction, eating, and drinking). It is believed that drugs such as cocaine and amphetamine directly stimulate these centers, while opiates free the pathways from inhibitory control. Nicotine, on the other hand, reaches the brain in as little as 10-20 seconds, where it stimulates nicotine receptors to cause dopaminergic neurons to release large quantities of dopamine. After a few hours, dopamine levels decline, causing withdrawal symptoms to readily appear (e.g., anxiety, irritability, and inattentiveness). When cigarette smokers say they need a smoke to steady their nerves, what they really mean is that they have to contend with nicotine withdrawal. 

In order to distinguish specific effects on reinforcement from nonspecific effects on performance various studies on the effect of DA receptor blockers and 6-OHDA lesions on opiate self-administration have looked for an increase in responding in fixed-ratio... 

Studies with complex schedules of multiple reinforcement for drug, food and water have similarly shown that 6-OHDA lesions that shift to the right the dose-response function for cocaine, do not affect that for opiate or food responding (Dworkin et al., 1988) thus contradicting an earlier study reporting an impairment of opiate selfadministration by 6-OHDA lesions (Smith et al., 1985). 

Therefore, self-administration studies do not provide any evidence for a specific role of DA in opiate reinforcement and on this basis it has been concluded that DA does not play a role in the reinforcing properties of opiates (Ettenberg et al., 1982 Pettit et al., 1984 Van Ree and Ramsey, 1987 Gerrits et al., 1994). 

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