Psychostimulant self-administration

The above framework forms the basis for interpreting the effect of experimental manipulation of DA transmission on responding for cocaine self-administration. Neuroleptics reduce responding on the ascending limb of the bell-shaped dose-response curve while they increase responding on the descending limb (Wilson and Schuster, 1972  

Notably, in the monkey, at variance with the rat (Koob et al., 1987), SCH 23390 fails to increase responding on FR schedules with (Woolverton and Virus, 1989) and without (Woolverton, 1987) a time-out period moreover, acute SCH 23390 (Woolverton and Virus, 1989) and neuroleptics (Woolverton and Balster, 1981) fail to specifically impair cocaine reinforcement as they also reduce responding for food. 

Evidence for a role of NAc DA in cocaine reinforcement has been provided by studies of the effect of 6-OHDA lesions on cocaine self-administration. Thus, 6-OHDA lesions of the DA innervation of the nucleus accumbens result in extinction-like effects on responding for cocaine in FR schedules (Roberts et al., 1977 Roberts et al., 1980, Pettit et al., 1984) and in a decrease in break point in progressive ratio schedules (Koob et al., 

In contrast, 6-OHDA lesions of the prefrontal cortex, an area where cocaine is self-infused (Goeders and Smith, 1983 Goeders et al., 1986), fail to reduce (Martin-Iverson et al., 1986) or actually increase (Schenk et al., 1991) cocaine self-administration. 

Studies with amphetamine also show extinction-like effects of neuroleptics, with an increased rate of responding followed by a reduction to saline values (Balster and Schuster, 1973a Yokel and Wise, 1975, 1976 Risner and Jones, 1976). Extinction of responding for amphetamine is also specifically induced by 6-OHDA lesions of the DA innervation of the NAc (Fyness et al., 1979). 

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Self-administration of psychostimulants by humans produces a syndrome of intoxication, the symptoms of which can include elevated pulse and blood pressure, pupillary dilation, euphoria, and psychomotor agitation. Ingestion of excessive amounts can result in compulsive behavior, psychotic symptoms that include auditory and visual hallucinations and paranoid delusions, chest pain, arrhythmias, dyskinesias, and seizures. 

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. 

Recent studies have also evaluated the interaction between cannabinoids and other psychostimulants such as amphetamine and MDMA (methylenedioxymethamphetamine ecstasy) (Braida and Saia 2002 Parker et al. 2004). These studies showed that infusion of the cannabinoid agonist CP55,940 decreased intracere-broventricular MDMA self-administration in rats (Braida and Saia 2002). It remains to be determined, however, if cannabinoids modulate the addictive properties of psychostimulant drugs. 

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