Potentiation of intracranial self-stimulation during prolonged subcutaneous infusion of cocaine

Subcutaneous administration of cocaine yields a longer duration of action than administration via the intraperitoneal or intravenous routes. However, cocaine is a powerful vasoconstrictor, and thus injection of this drug at a single subcutaneous locus entails significant risk of necrotic skin lesions. This paper introduces a new method for subcutaneous administration of cocaine that reduces the probability of dermonecrosis by dispersing the drug under a large area of skin. Two experiments were conducted to evaluate the new method. In the first, changes in dopamine tone in the nucleus accumbens were measured by means of microdialysis during prolonged subcutaneous infusions of cocaine. The dopamine concentration attained a fairly stable, elevated level, suggesting that absorption, distribution, and excretion of the drug approached steady state. In a second experiment, performance for rewarding electrical stimulation was measured during repeated prolonged infusions of cocaine. The pulse frequency required to sustain responding was decreased by the drug, in a manner that was stable both within and across test sessions. Thus, the new method is appropriate for studies requiring stable neurochemical and behavioral conditions during repeated long test sessions, high rates of drug delivery and alternation between administration of the drug and the vehicle.