Factors affecting the regulation of intravenous drug self -administration by the rhesus monkey.

It has been suggested that the motivation (of both humans and animals) to self-administer drugs is governed by a homeostatic mechanism that acts to achieve and maintain a constant level of circulating drug in the brain. This notion is both central to a prominent contemporary theory of drug addiction (the reward-allostasis model) and has for decades been the source of considerable confusion in the ethanol self-administration literature, as animals invariably self-administer between 300--400% more ethanol by the intravenous route than they do by the oral route. Data obtained in this thesis demonstrate the existence of a stable ascending limb to the dose-response curve for intravenously self-administered ethanol, cocaine, and dilaudid on a continuous schedule of reinforcement in which increases in response rate result in an increased rate of drug intake. These data make it clear that the attainment and maintenance of a threshold level of drug in the brain is not a necessary component of an animal's motivation to self-administer it. Instead, at the relatively low doses that comprise the ascending limb of this function (which include those used in the oral ethanol self-administration paradigm), an increase in dose is accompanied by an increase in the rate of intake. This phenomenon may be due to the fact that with larger doses, a given drug effect can be achieved more rapidly than with smaller doses, and that, at low drug doses, faster rates of drug accumulation may impart a greater degree of reinforcing efficacy. Support for this possibility comes from a finding of this thesis that, with dose held constant, an increase in the rate of intravenous infusion engendered significantly more rapid rates of responding and consequently, more rapid rates of drug intake.Ph.D.Experimental psychologyPsychobiologyPsychologyUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/124786/2/3163796.pd