The Effects of Cocaine Preexposure on the Acquisition of Cocaine-Induced Taste Aversions

Rats preexposed to MDMA display attenuated responses to its aversive effects in the absence of persistent monoamine depletions

“…It is important to note in this context that the US preexposure effects observed with other psychoactive drugs are comparable to those observed here and generally do not result in a complete abolition of aversions (Berman and Cannon 1974;Cappell and Le Blanc 1975;Riley and Diamond 1998;Riley and Simpson 1999;Simpson and Riley 2005;Davis and Riley 2007). In contrast, the US preexposure effects observed with classical emetics (e.g., LiCl, apomorphine) are generally quite robust, often resulting in the complete loss of taste aversion induction by the drug (Brookshire and Brackbill 1976;Cain and Baenninger 1977;Cannon et al 1977).…”

“…Similar findings with other drugs are commonly described in terms of pharmacological tolerance (i.e., the perceived aversive effects associated with the drug may be reduced over repeated administrations) (Cappell and Le Blanc 1975;Riley et al 1976;Riley and Diamond 1998;Davis and Riley 2007; although see Batson and Best 1979;de Brugada et al 2003 for alternative interpretations of the US preexposure effect based on associative learning). This interpretation of our findings is supported by previous research showing tolerance to many of the effects of MDMA, including behavioral tolerance to its reinforcing effects (Fantegrossi et al 2004), MDMA-induced cognitive impairments (Frederick et al 1995) and hyperactivity (Callaway and Geyer 1992;Brennan and Schenk 2006), as well as physiological tolerance to MDMA-induced serotonin syndrome (Marston et al 1999;Shankaran and Gudelsky 1999;Piper et al 2005) and temperature dysregulation (Shankaran and Gudelsky 1999;Piper et al 2005;Piper et al 2006).…”

“…Immediately following this access, subjects were rank-ordered according to their water consumption and assigned to one of two groups (M and V; n=17 and 16, respectively). Four to five hours following this water access (a time interval previously used in CTA preexposure assessments, e.g., Riley and Diamond 1998), subjects in group M were administered MDMA (1.8 mg/kg) and subjects in group V were administered vehicle (equivolume to the MDMA injections). This dose was chosen to be comparable to that used during conditioning (see below).…”

“…In general, aversions are attenuated if exposure to the drug is given prior to taste-aversion conditioning, a phenomenon termed the unconditioned stimulus (US) preexposure effect. Initially displayed using classical emetics such as lithium chloride (Brookshire and Brackbill 1976;Elkins 1974), this effect has been observed in taste-aversion learning with a variety of compounds, notably including a host of abused drugs, e.g., ethanol, cocaine, morphine and D-amphetamine (Berman and Cannon 1974;Goudie and Thornton 1975;Riley et al 1984;Riley and Diamond 1998). Given that the taste-aversion preparation may provide a sensitive index of aversive drug properties (Cunningham et al 2000;Shram et al 2006;Diaz-Granados and Graham 2007;Rinker et al 2008), such findings suggest that for many drugs of abuse, prior drug history may weaken the drug"s aversive effects, increasing its abuse potential, i.e., the relative balance between the drug"s rewarding and aversive effects is shifted (Wise et al 1976;Lynch and Carroll 2001;Riley et al 2009).…”

Effects of 3,4-methylenedioxypyrovalerone (MDPV) pre-exposure on the aversive effects of MDPV, cocaine and lithium chloride: Implications for abuse vulnerability

“…One that has received increasing attention in this context is drug history. For example, rats with prior exposure to cocaine display sensitized conditioned place preferences (Lett, 1985) and attenuated taste avoidance (Riley and Diamond, 1998), indicative of changes in the rewarding and aversive effects of the drug, respectively. Such sensitizing (Koob and LeMoal, 2005) and attenuating (Randich and LoLordo, 1979; Riley and Simpson, 2001) effects of drug history have been reported for a variety of drugs.…”