Histamine antagonists often have troublesome side effects in therapeutic application and may be used illicitly in combination with other drugs (e.g., """"""""T's and Blues"""""""") by certain drug-dependent populations. Preliminary results from our laboratory indicate that selected histamine antagonists can have pronounced behavioral effects in monkeys and, like prototypical drugs of abuse, can maintain persistent drug-taking behavior. The objective of the proposed research is to identify pharmacological and environmental factors that determine how these drugs affect behavior. The actions of histamine H-1 and H-2 antagonists on scheduled-controlled behavior will be studied by determining their effects on suppressed and nonsuppressed responding under different environmental conditions, by comparing their effects with the effects of drugs from other pharmacological classes, and by comparing their effects when administered by central and peripheral routes. The reinforcing actions of histamine antagonists will be studied by determining their effects in initiating and maintaining self-administration behavior, by comparing their effects with the reinforcing effects of other drugs, by determining the functional characteristics of environmental stimuli associated with their injection, and by determining the effects of self-administered drugs on other ongoing behavior. Interactions between histamine antagonists and frequently co-administered drugs will be studied by determining how histamine antagonists modify the effects of selected opiates, such as morphine and pentazocine, and selected benzodiazepines, such as diazepam. Overall, the proposed research will provide fundamental information about the actions of histamine antagonists in altering and controlling behavior.
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