Effects of a partial dopamine D2-like agonist on the cocaine-induced behavioral sensitization of preweanling rats.

Partial D(2)-like receptor agonists act as functional antagonists when given during periods of high dopaminergic tone (e.g., when self-administering cocaine or amphetamine). For this reason, we determined whether pretreatment with the partial D(2)-like agonist terguride would block the induction and/or expression of cocaine-induced behavioral sensitization in preweanling rats. More specifically, we examined (a). whether repeated administration of terguride alone (0.4-1.6 mg/kg) would support behavioral sensitization (Experiment 1); (b). whether injecting preweanling rats with terguride (0.1-1.6 mg/kg) during the pretreatment phase would block the induction and ultimate expression of cocaine-induced behavioral sensitization (Experiment 2); and (c). whether injecting rats with terguride (0.2-0.8 mg/kg) on the test day would block the expression of cocaine sensitization (Experiment 3). Results showed that repeated terguride administration did not induce behavioral sensitization by itself, nor did it block the induction of cocaine sensitization in preweanling rats. Interestingly, terguride reduced, but did not fully attenuate, the locomotor activity of cocaine-treated rats during the pretreatment phase. When given on the test day, terguride also depressed cocaine-induced locomotor activity, but rather than blocking the expression of behavioral sensitization, terguride seemed to cause a general reduction in locomotion. Because partial D(2)-like agonists attenuate cocaine- and amphetamine-induced reward, it has been proposed that this class of drug might serve as an effective pharmacotherapy for psychostimulant abuse. Although partial D(2)-like agonists may prove useful in this regard, results from the present study suggest that terguride would not block sensitization components of the addiction process.