Individual differences in cocaine discrimination

Abstract

Goudie, A.J., M. Leathley, J. McNally, and C.R. West: Individual differences in cocaine discrimination. Drug Dev. Res. 16:123-131, 1989. This study involved an attempt to develop a screening test to select animals that would learn a cocaine drug discrimination (DD) rapidly and an analysis of factors affecting rates of acquisition of cocaine DD. Rats (n = 18) were trained initially in a conditioned taste aversion (C.T.A.) procedure with cocaine (36 mgikg). Subjects were then trained to discriminate cocaine (5 mgikg) in an operant procedure, and the cocaine generalization curve was determined. Subjects were then tested for cocaine-induced hyperthermia. Animals that showed weak C.T.A. showed relatively rapid acquisition of DD (r, = -0.56, P < 0.05, two tailed). Cocaine-induced hyperthermia did not predict speed of acquisition reliably, nor did cocaine's effects on operant responding. Animals were allocated retrospectively to groups of "rapid" and "slow" discriminators. These groups did not differ in generalization EDSOs, in sensitivity to cocaine's effects on operant responding, or in hyperthermic responses to cocaine. Thus speed of DD acquisition was not dependent on individual sensitivity to cocaine. Furthermore, "rapid" and "slow" discriminators probably cannot be dissociated in terms of learning ability, since animals that acquired marked C.T.A. showed slow learning of DD. The C.T.A. data suggest that animals sensitive to dysphoric effects of cocaine are less sensitive to the drug's cueing properties and thus that the cocaine cue at 5 mgikg may be related to its euphoriant actions. It is possible that C.T.A. procedures can be used to select animals that will learn cocaine DD rapidly.

Effects of Methylone Pre-Exposure on Fluoxetine-Induced Conditioned Taste Avoidance in Male and Female Sprague-Dawley Rats

“…Interestingly, MK 212 only partially attenuated the aversive effects of the 5-HT 7 /5-HT 1A receptor agonist 8-OH-DPAT (and no attenuation on the moderately selective 5-HT 2A agonist DOI), suggesting that fluoxetine’s stimulus effects may be mediated primarily by 5-HT activity at the 5-HT 2C receptor. Similar work assessing the effects of pre-exposure to other drugs on fluoxetine-induced avoidance is limited (see [ 20 ]; for a review, see [ 53 ]); however, drug discrimination learning (DDL) procedures that are also used to determine shared stimulus properties (albeit not necessarily those associated with the drugs’ aversive effects; see [ 54 ]) support the fact that fluoxetine’s stimulus effects are primarily mediated by its actions on 5-HT. Establishing discriminative control when fluoxetine is used as a training drug in the DDL procedure has proven difficult, likely due to its long half-life (see [ 55 ]; though see [ 56 ] for a discussion of other SSRIs that have been successfully demonstrated in this design); however, several studies have demonstrated that fluoxetine generalizes to serotonergic compounds ([ 57 , 58 ]; though see [ 59 ]) and potentiates the discriminability of several compounds with serotonergic activity [ 58 , 60 , 61 ].…”