Role of training dose in drug discrimination

Abstract

Drug discrimination has been an important technique in behavioural pharmacology for at least 40 years. The characteristics of drug-produced discriminative stimuli are influenced by behavioural and pharmacological variables, including the doses used to establish discriminations. This review covers studies on the effects of varying the training dose of a drug in a search for general principles that are applicable across different drug classes and methodological approaches. With respect to quantitative changes, relationships between training dose and rate of acquisition or magnitude of stimulus control were found for most drug classes. Acquisition accelerated with dose up to a point beyond which drug-induced impairments of performance had a deleterious impact. Sensitivity to the training drug as measured by ED50 values typically increased when the training dose was reduced. Qualitative changes were more complex and appeared to fall into three categories: (i) changes in profiles of generalisation between partial and full agonists; (ii) reduced specificity of some discriminations at small training doses and (iii) changes in the relative salience of actions mediated through different neurotransmitter systems or from central and peripheral sites. Three-lever discrimination procedures incorporating ‘drug versus drug’ or “dose versus dose” contingencies enabled detection of more subtle differences than the simple ‘drug versus no drug’ approach when applied to the opioid, hallucinogen and barbiturate classes of drugs. These conclusions have implications for the interpretation of data from studies that utilise either within- or between-subject designs for studying the discriminative stimulus effects of drugs.

Stress Hormone Exposure Reduces mGluR5 Expression in the Nucleus Accumbens: Functional Implications for Interoceptive Sensitivity to Alcohol

“…Further, sensitivity to a moderate alcohol dose (1 g/kg) can be restored by pharmacological activation of mGluR5, perhaps suggesting alleviation, in part, of the functional consequence of downregulated mGluR5. Importantly, alcohol is a complex stimulus cue and different receptor systems modulate sensitivity to different alcohol doses (eg, high vs low; cf, Grant, 1999;Stolerman et al, 2011). Therefore, it will be important to extend the present findings to higher alcohol training doses.…”

Combined effects of modafinil and d-amphetamine in male Sprague–Dawley rats trained to discriminate d-amphetamine

“…A recent comprehensive review by Stolerman et al (2011) summarizes several key principles derived from research on the role of training dose in drug discrimination. Notably, higher training doses tend to produce enhanced discrimination accuracy, whereas lower training doses tend to produce lower ED 50 values with the training drug and enhanced sensitivity in stimulus generalization tests with other test compounds.…”

Predicting abuse potential of stimulants and other dopaminergic drugs: Overview and recommendations

“…One of those factors is the dose of the drug used for training (see Stolerman et al, 2011 for a recent review). For example, Schechter (1997) found that the dose-effect functions for cocaine, d- amphetamine, and methamphetamine were shifted to the left in rats trained to discriminate a low dose (2.0 mg/kg) relative to a high dose of cocaine (10.0 mg/kg) from saline.…”