The overall aims of this project are to characterize certain of the behavioral effects of representative opioid drugs, to compare these effects with similar actions of drugs of other classes (alpha2-adrenoreceptor agonists, serotonin agonists, and histamine H1 antagonists), and to identify significant interactions in the behavioral effects of these drugs. A working hypothesis of the project is that valuable basic information, relevant both to drug abuse and to fuller understanding of neurotransmitter participation in the control of behavior, will come from work of this nature. Three general types of experiments will be done. First, because certain of the behavioral effects of acutely administered opioids, alpha2 agonists such as clonidine, and serotonin agonists are similar, one series of experiments will determine the extent to which tolerance to the behavioral effects of one of these drugs is transferred to drugs of the other two classes (cross-tolerance). In these and other experiments, responding under various schedules of reinforcement and under electrical-stimulus titration procedures will be studied in rats and squirrel monkeys. A second series of experiments will focus on behavioral sequelae of changes in CNS serotonin activity, and the possible role such changes might play in mediation of the behavioral effects of opioid drugs. There will also be studies of the possible role of dopamine in mediation of certain of the behavioral effects of serotonin agonist drugs. A final series of experiments will focus on the behavioral effects of histamine H1 antagonists, given both alone and in combination with opioid drugs. Drugs of this class are among the most widely taken, generally under minimal medical supervision, and there are recent reports of significant interactions in the effects of antihistamines and opioid drugs both in experimental animals and humans.
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