Psychomotor stimulant self administration as a function of dosage per injection in the Rhesus monkey

Abstract

The relationships between drug dosage per injection and response rate, and drug dosage per injection and total daily drug intake were ascertained in Rhesus monkeys which self-administered cocaine, pipradrol, methylphenidate and phenmetrazine intravenously. The study demonstrated the monkeys would selfadminister all of these compounds over a wide range of dosages. Furthermore, the magnitude of reinforcement, i.e., dosage per injection, and the rate of responding in self-administering these compounds were inversely related. However, total daily drug intake was independent of the dosage per injection over a wide range of dosages. The results indicate that either the subjects can compensate for large changes in unit dosage so that daily drug intake remains stable or that a direct effect of these compounds functions in limiting their self-administration.

FIXED‐INTERVAL SCHEDULE OF COCAINE REINFORCEMENT: EFFECT OF DOSE AND INFUSION DURATION1

“…The effect of unit dose on rate of cocaine self-administration has also been studied by Pickens and Thompson (1968a) with rats and by Wilson, Hitomi, and Schuster (1971) and Goldberg, Hoffmeister, Schlichting, and Wuttke (1971) with monkeys. These studies utilized a CRF schedule of reinforcement.…”

“…An inverse relationship between response rate and magnitude of drug reinforcement (dose per infusion) has been found using d-amphetamine (Pickens and Harris, 1968), methamphetamine (Pickens, Meisch, and McGuire, 1967), cocaine (Pickens and Thompson, 1968a;Woods and Schuster, 1968), and methylphenidate, pipradol, and phenmetrazine (Wilson, Hitomi, and Schuster, 1971). All of the studies utilized a continuous schedule of reinforcement (CRF) where an increase in rate is accompanied by an increase in drug intake.…”

The Motivation to Self-Administer is Increased After a History of Spiking Brain Levels of Cocaine

“…Brain concentrations of cocaine rose relatively rapidly in all groups at the beginning of the session. This wellcharacterized phenomenon has been referred to as a loading phase (Wilson et al, 1971), and is typically followed by a maintenance phase during which drug levels are maintained within relatively narrow limits. In this study, four groups were allowed to progress into the maintenance phase for varying lengths of time.…”

“…This procedure has been shown to produce a robust escalation in drug intake (B30-40%) over a 2-week period, which is not observed in short access (ShA) controls given access to only 1 h/day (Ahmed and Koob, 1998). These sessions, and all FR1 sessions, typically show a loading and maintenance phase (Ettenberg et al, 1982;Wilson et al, 1971). That is, animals load up at the beginning by self-administering several injections in a short period of time, and for the remainder of the session, infusions become more evenly spaced resulting in cocaine levels being maintained within relatively narrow limits (Ahmed and Koob, 2005).…”

N-Acetylcysteine as a Treatment for Addiction

“…This self-administration procedure is particularly useful in determining the abuse liability of psychoactive substances (for a review see O'Connor et al, 2011). The ability to self administer drugs for short periods of time daily (1-2 hrs per session) results in a stable drug intake over time, a so-called titration process that is suggested to reflect individual control of intake responding to optimal dosing (Wilson et al, 1971;Zimmer et al, 2011) around which blood levels fluctuate in the course of the selfadministration session.…”