Once is too much: Conditioned aversion develops immediately and predicts future cocaine self-administration behavior in rats.

Colechio, Elizabeth M.; Imperio, Caesar G.; Grigson, Patricia S.

doi:10.1037/a0036264

Cited by 23 publications

(24 citation statements)

References 48 publications

(93 reference statements)

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“…Kasanetz et al (2010) drew a similar conclusion by measuring persistence in responding during the latter part of the non-drug periods. Finally, Colechio et al (2014) showed that early orofacial responses to a cocaine-paired taste cue could predict later differences in responding for cocaine following a single taste-drug pairing. Vulnerability for addiction, then, can potentially be evidenced very early on and the effect grows with experience, particularly for some rats.…”

Section: Discussionmentioning

confidence: 99%

Low expression of D2R and Wntless correlates with high motivation for heroin.

Tacelosky¹,

Alexander²,

Morse³

et al. 2015

Behavioral Neuroscience

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Drug overdose now exceeds car accidents as the leading cause of accidental death in the U.S. Of those drug overdoses, a large percentage of the deaths are due to heroin and/or pharmaceutical overdose, specifically misuse of prescription opioid analgesics. It is imperative, then, that we understand the mechanisms that lead to opioid abuse and addiction. The rewarding actions of opioids are mediated largely by the mu opioid receptor (MOR), and signaling by this receptor is modulated by various interacting proteins. The neurotransmitter dopamine also contributes to opioid reward, and opioid addiction has been linked to reduced expression of dopamine D2 receptors (D2R) in brain. That said, it is not known if alterations in the expression of these proteins relates to drug exposure and/or to the “addiction-like” behavior exhibited for drug. Here, we held total drug self-administration constant across acquisition and showed that reduced expression of the D2R and the MOR interacting protein, Wntless, in the medial prefrontal cortex was associated with greater “addiction-like” behavior for heroin, in general, and with a greater willingness to work for drug, in particular. In contrast, reduced expression of the D2R in the nucleus accumbens and hippocampus was correlated with greater seeking during signaled non-availability of drug. Taken together, these data link reduced expression of both the D2R and Wntless to the explicit motivation for drug, rather than to differences in total drug intake, per se.

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Section: Discussionmentioning

confidence: 99%

Low expression of D2R and Wntless correlates with high motivation for heroin.

Tacelosky¹,

Alexander²,

Morse³

et al. 2015

Behavioral Neuroscience

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“…Drugs of abuse have both rewarding and aversive effects (Cunningham, 1979; Turenne et al, 1996; Verendeev and Riley, 2011), and it is the balance of these two affective properties that impact their use and abuse (Colechio et al, 2014; Riley et al, 2009; Stolerman, 1985; Wise et al, 1976). One class of drugs only beginning to be examined in this context are the synthetic cathinones (Al-Juhaishi et al, 2012; Busardo et al, 2015; Kalix, 1992; Patel, 2000).…”

Section: Introductionmentioning

confidence: 99%

Conditioned taste avoidance, conditioned place preference and hyperthermia induced by the second generation ‘bath salt’ α-pyrrolidinopentiophenone (α-PVP)

Nelson

Hempel

Clasen

et al. 2017

Pharmacology Biochemistry and Behavior

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Background α-pyrrolidinopentiophenone (α-PVP) has been reported to be rewarding in a variety of pre-clinical models. Given that a number of drugs of abuse have both rewarding and aversive effects, the balance of which influences addiction potential, the present study examined the aversive properties of α-PVP by assessing its ability to induce taste avoidance. This assessment was made in a combined taste avoidance/place conditioning design that also allowed an evaluation of the relationship between α-PVP’s aversive and rewarding effects. Methods Male Sprague-Dawley rats were exposed to a novel saccharin solution, injected with one of four doses of α-PVP (0, 0.3, 1.0 and 3.0 mg/kg) (IP) and placed on one side of a place conditioning apparatus. The next day, they were injected with vehicle, given access to water and placed on the other side. Following four conditioning cycles, saccharin avoidance and place preferences were then assessed. The effects of α-PVP on body temperature were also examined. Results α-PVP induced dose-dependent taste avoidance as well as significant increases in time spent on the drug-paired side (although this effect was not dependent on dose). α-PVP also induced dose- and time-dependent hyperthermia. Conclusions α-PVP induced significant taste avoidance whose strength relative to the psychostimulants methylenedioxypyrovalerone (MDPV) and cocaine paralleled their relative binding to the dopamine transporter. Similar to other drugs of abuse, α-PVP has both aversive and rewarding effects. It will be important to assess how various experiential and subject variables impact these effects and their balance to predict abuse liability.

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“…Drugs of abuse have both rewarding and aversive effects, and it is the balance of these two affective properties that impact the use and abuse of these compounds (Colechio et al, 2014; Riley et al 2009; Stolerman, 1985; Wise et al, 1976). Understanding this relative balance and the factors that influence it may be critical in predicting vulnerability to the drug’s use and abuse (Cunningham et al, 2009; Riley, 2011).…”

Section: Introductionmentioning

confidence: 99%

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

Woloshchuk

Nelson

Rice

et al. 2016

Drug and Alcohol Dependence

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Background Drug use is thought to be a balance of the rewarding and aversive effects of drugs. Understanding how various factors impact these properties and their relative balance may provide insight into their abuse potential. In this context, the present study attempted to evaluate the effects of drug history on the aversive effects of 3,4-methylenedioxypyrovalerone (MDPV), one of a variety of synthetic cathinones (collectively known as “bath salts”). Methods Different groups of male Sprague-Dawley rats were exposed to either vehicle or MDPV (1.8 mg/kg) once every fourth day for five total injections prior to taste avoidance conditioning in which a novel saccharin solution was repeatedly paired with either vehicle, MDPV (1.8 mg/kg), the related psychostimulant cocaine (18 mg/kg) or the emetic lithium chloride (LiCl) (13.65 mg/kg). Results In animals pre-exposed to vehicle, all three drugs induced significant and comparable taste avoidance relative to animals injected with vehicle during conditioning. MDPV pre-exposure attenuated the avoidance induced by both MDPV and cocaine (greater attenuation for MDPV than cocaine), but had no effect on that induced by LiCl. Conclusions These findings suggest that a history of MDPV use may reduce or attenuate MDPV and cocaine’s (but not LiCl’s) aversive effects. The implications for such changes in MDPV’s aversive effects to its potential use and abuse were discussed.

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Once is too much: Conditioned aversion develops immediately and predicts future cocaine self-administration behavior in rats.

Cited by 23 publications

References 48 publications

Low expression of D2R and Wntless correlates with high motivation for heroin.

Low expression of D2R and Wntless correlates with high motivation for heroin.

Conditioned taste avoidance, conditioned place preference and hyperthermia induced by the second generation ‘bath salt’ α-pyrrolidinopentiophenone (α-PVP)

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

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