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

Abstract

Rhesus monkeys were trained on a fixed-interval 9-min limited-hold 3-min schedule of intravenous cocaine reinforcement. A 15-min timeout followed each reinforcement or limitedhold expiration. An identical schedule of food reinforcement was interspersed in the session to assess rate-modifying effects of the drug infusions not specific to drug reinforcement. In one experiment, response rate for cocaine reinforcement was shown to be a positive function of reinforcement magnitude for a dose range from 0 to 800 ug/kg/inj. At these doses, there was little effect on food reinforced responding except at the highest dose, where responding decreased. Results of the second experiment indicated that increasing the duration of the cocaine infusion produced a change in response rate similar to decreasing unit dose. The response rate change for a given increase in infusion duration was less at a unit dose of 400 ug/kg than at 200 ug/kg.

Faster onset and dopamine transporter selectivity predict stimulant and reinforcing effects of cocaine analogs in squirrel monkeys

“…oral) resulting in slower drug uptake (Volkow et al, 2000). When cocaine was infused more slowly, it was found to be less effective as a reinforcer in nonhuman primates (Balster and Schuster, 1973;Panlilio et al, 1998). Similarly, the cocaine analog HD-23, which takes 60 min to attain significant binding was not as reinforcing in rhesus monkeys as were cocaine or methylphenidate (Lile et al, 2003).…”

Toluene-Induced Locomotor Activity is Blocked by 6-Hydroxydopamine Lesions of the Nucleus Accumbens and the mGluR2/3 Agonist LY379268

“…Moreover, the reinforcement produced by such psychoactive substances is related to changes in drug concentration in the brain rather than to steady-state blood levels (Balster and Schuster, 1973). Rapid changes in brain concentrations are also reflected as having greater reinforcement efficacy and, in fact, with increasing exposure durations, drug reinforcement responses show a change in response rates similar to a decrease in unit dose (Balster and Schuster, 1973).…”

“…Moreover, the reinforcement produced by such psychoactive substances is related to changes in drug concentration in the brain rather than to steady-state blood levels (Balster and Schuster, 1973). Rapid changes in brain concentrations are also reflected as having greater reinforcement efficacy and, in fact, with increasing exposure durations, drug reinforcement responses show a change in response rates similar to a decrease in unit dose (Balster and Schuster, 1973). As the behavioral effects of a drug must ultimately result from some alteration in neuronal activity, it is particularly interesting that abuse-relevant concentrations of toluene in the blood (B300 mM) are very efficacious at stimulating VTA DA neuronal activity both in vivo andin vitro: an effect principally observed during transient (seconds to minutes) 'pulses' of the solvent French, 1999a, 2002).…”

Effects of Low- and High-Nicotine Cigarette Smoking on Mood States and the HPA Axis in Men

“…nicotine is self-administered by humans and experimental animals under a number of conditions (Goldberg et al, 1981;Spealman and Goldberg, 1982;Henningfield and Goldberg, 1983;Corrigall, 1999;Donny et al, 1999;Harvey et al, 2004). With nicotine, as with many abused drugs, speed of the injection is an important determinant of relative reinforcing efficacy (Balster and Schuster, 1973;Wakasa et al, 1995;Abreu et al, 2001). The reinforcing effects of nicotine are mediated, in part, by stimulating nicotinic acetylcholine receptors on mesolimbic dopamine neurons to release dopamine (Fu et al, 2000;Gerasimov et al, 2000;Watkins et al, 2000).…”