Early avoidance of a heroin-paired taste-cue and subsequent addiction-like behavior in rats

Abstract

The ability to predict individual vulnerability to substance abuse would allow for a better understanding of the progression of the disease and development of better methods for prevention and/or early intervention. Here we use drug-induced devaluation of a saccharin cue in an effort to predict later addiction-like behavior in a model akin to that used by Deroche-Gamonet et al. (2004) and seek to link such vulnerability to changes in expression of various mu opioid receptor and D2 receptor-interacting proteins in brain. The results show that the greatest heroin-induced suppression of intake of a saccharin cue is associated with the greatest vulnerability to later addiction-like behavior and to differences in the expression of WLS, β-catenin, and NCS-1 in brain compared to rats that exhibited the least suppression of intake of the heroin-paired cue and/or saline controls. Finally, because the self-administration model employed produced no significant differences in drug intake between groups, overall, the resultant changes in protein expression can be more closely linked to individual differences in motivation for drug.

Nicotine pre-treatment reduces sensitivity to the interoceptive stimulus effects of commonly abused drugs as assessed with taste conditioning paradigms

“…Many commonly abused drugs paradoxically increase the incentive salience of contextual stimuli (Berridge and Robinson, 1998; Flagel et al, 2009; Robinson et al, 2015; Uslaner et al, 2006) while simultaneously conditioning avoidance responses to paired orosensory stimuli (Imperio and Grigson, 2015; Jenney et al, 2016; Liu et al, 2009; Parker, 1995, 2003). This is in contrast to the effects of primarily emetic stimuli, such as lithium chloride (LiCl), which result in both conditioned place and taste avoidance (CPA and CTA, respectively; Parker, 2003; Tenk et al, 2005, 2006).…”

“…Conversely, drug self-administration under some conditions can increase the acceptance of paired orosensory stimuli (Loney and Meyer, 2018), as defined by a relative reduction in rejection, suggestive of an increase in palatability. These positive and negative changes in hedonic stimulus value, (i.e.,, conditioned taste revaluation; CTR) are often used to assess sensitivity to drug reinforcement (Imperio and Grigson, 2015; Jenney et al, 2016), and can be used to infer changes in the interoceptive stimulus properties of a given drug. Both avoidance and appetitive CTR is dependent on the interoceptive stimulus properties of the unconditioned stimulus (US); exteroceptive stimuli (e.g., foot shock, acoustic startle) do not result in a revaluation of taste stimuli (Garcia and Koelling, 1966).…”

Identifying novel members of the Wntless interactome through genetic and candidate gene approaches

“…This pathway has also been shown to be involved in maintenance of adult tissues and its dysregulation has been implicated in several disease states including cancer, neurological disorders, neurodegenerative diseases, and addiction (Cuesta et al, 2016; Cuesta et al, 2017; Dias et al, 2015; Jenney et al, 2016; Jin et al, 2010a; Petko et al, 2013; Tacelosky et al, 2015). …”

“…Several recent studies have shown that Wls protein levels are altered in animals that are exposed to morphine pellets (experimenter administered) or in rats that exhibit addiction-like behaviors for heroin in self-administration paradigms (Herrero-Turrion et al, 2014; Jenney et al, 2016; Petko et al, 2013; Tacelosky et al, 2015). These results provide support for the idea that opioids may serve to alter Wnt secretion and signaling, as well as some of the neural changes that accompany opioid addiction.…”

Addiction: A preclinical and clinical analysis

“…The final set of research papers address drug-induced devaluation of natural rewards in a rodent model and in recovering human opioid addicts. In an effort to better understand how one model of addiction interfaces with another, Jenney et al [in this issue] test whether large suppressors of the heroin-paired saccharin cue following just 3 taste-drug pairings will evidence high ‘addiction-like’ behavior when tested with intermittent drug access in a variation of the model used by Deroche-Gamonet et al [2004]. Jenney’s study goes on to link these differences in behavior to differences in the expression of mu opioid receptor interacting proteins (MORIPs) and a D2 receptor interactor in the prefrontal cortex, nucleus accumbens, hippocampus, and ventral tegmental area.…”