Opiate self-administration

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). 

In contrast with the reports that neuroleptics and 6-OHDA lesions impair acquisition of place preference conditioned by opiates, DA receptor blockers failed to impair the acquisition of opiate self-administration except at doses that nonspecifically impaired responding (Van Ree and Ramsey, 1987 Gerrits et al., 1994). 

In D2 KO mice conflicting results have been obtained on a place preference paradigm. In morphine-naive mice Maldonado et al. (1997) reported an impairment of morphine-conditioned place preference while Dockstader et al. (2001) did not. Curiously morphine-conditioned place preference was impaired in morphine-dependent D2 KO mice. 

Genetic deletion of D2 receptors disrupted instrumental responding for i.v. morphine (Elmer et al., 2002). However the specificity of this effect is questionable as the acquisition of instrumental responding for water was also reduced. 

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Gratton, Alain. 1996. "In Vivo Analysis of the Role of Dopamine in Stimulant and Opiate Self-Administration." Journal of Psychiatry and Neuroscience 21 264-79. 

The neuroehemical sites for psyehomotor stimulant reward are likely to be the presynaptic dopamine terminals located in the region of the nucleus aeeumbens, frontal cortex, and other forebrain structures that originate in the ventral tegmental area. Note, however, that intraeranial self-administration of eoeaine is elicited from the frontal cortex, but not from the nucleus aeeumbens (Goeders and Smith 1983). Thus, eoneomitant activation of structures other than the nucleus accumbens may be an important part of the circuitry involved in initiation of cocaine intravenous self-administration, as has been hypothesized for the opiates (Smith and Lane 1983 Smith et al. 1982). 

Smith, J.E., and Lane, J.D. Brain neurotransmitter turnover correlated with morphine self-administration. In Smith, J.E., and Lane, J.D., eds. The Neurobiology of Opiate Reward Processes. Amsterdam Elsevier, 1983. pp. 361402. 

Do not try to overcome reversal of opiate effects by self-administration of large doses of narcotic... 

Suppression of heroin self-administration in opioid-dependent volunteers has been found to be greater at doses over lOOmg (Donny et al. 2005), and this relates to the three-level effects of methadone, the implications of which we often have to contend with in our discussions with patients. Basically low doses of methadone will suppress opiate withdrawal symptoms in dependent individuals, and this is what a lot of patients mean when they say that their dose (which may be considered too low by us) holds them. In medium to high levels of methadone there is less craving for opiates, and then at the highest doses there will be full narcotic blockade (Donny et al. 2002), but as already indicated the users themselves may not wish to take such dosages. 

Stewart, fane. 1983. "Conditioned and Unconditioned Drug Effects in Relapse to Opiate and Stimulant Drug Self-Administration." Progress in Neuropsychopharmacology and Biological Psychiatry 7 591-97. 

The study of the role of DA in ethanol self-administration is affected by problems not dissimilar from those encountered with other drugs of abuse except that, in contrast to the fair consistency in one direction or in the other among studies on psychostimulants and opiates, much disagreement is registered in the case of ethanol. 

Stewart J, de Wit H, Eikelboom R (1984) Role of unconditioned and conditioned drug effects in the self-administration of opiates and stimulants. Psychol Rev 97 251-268. 

In opiate abuse, smack ( junk, jazz, stuff, China white mostly heroin) is self administered by injection ( mainUning ) so as to avoid first-pass metabolism and to achieve a faster rise in brain concentration. Evidently, psychic effects ( kick, buzz, rush ) are especially intense with this route of administration. The user may also resort to other more unusual routes opium can be smoked, and heroin can be taken as snuff (B). 

The validity of these theoretically determined cutoff levels was evaluated by the various field studies described below. In some of these this involved comparing the results of hair analysis to those of urinalysis and self-reports. In the case of cocaine and morphine the validation of endogenous cutoff levels involved also the controlled administration of these substances. - With morphine this was done with poppy seed and involved a comparison of hair and urine results. These experiments clearly demonstrated the greater effectiveness of the endogenous cutoff levels used by hair analysis, for all attempts to exceed the opiate cutoff level of hair analysis by the massive ingestion of poppy seeds failed. In contrast to this, the cutoff level of urinalysis was exceeded by wide margins. That this particular problem of urinalysis is not unique to poppy seeds has been demonstrated experimentally by Baselt and Change in the case of cocaine. 

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