Modeling Relapse to Pavlovian Alcohol‐Seeking in Rats Using Reinstatement and Spontaneous Recovery Paradigms

LeCocq, Mandy Rita; Lahlou, Soraya; Chahine, Melanie; Padillo, Loreena Nadine; Chaudhri, Nadia

doi:10.1111/acer.13825

Cited by 19 publications

(21 citation statements)

References 49 publications

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“…However, home-cage alcohol intake at levels comparable to those in the present study can alter the motivational underpinnings of instrumental behaviour, rendering goal-directed responding habitual 63 . Also, ingested doses of alcohol within the range of what we report during Pavlovian conditioning result in detectable blood levels of alcohol 64 , suggesting that they produce pharmacological effects. Testing the effect of context on CS-triggered alcohol-seeking in alcohol-dependent rats as well as in female rats are two immediate future directions.…”

Section: Discussionsupporting

confidence: 50%

Dissociable mesolimbic dopamine circuits control responding triggered by alcohol-predictive discrete cues and contexts

et al. 2020

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Context can influence reactions to environmental cues and this elemental process has implications for substance use disorder. Using an animal model, we show that an alcohol-associated context elevates entry into a fluid port triggered by a conditioned stimulus (CS) that predicted alcohol (CS-triggered alcohol-seeking). This effect persists across multiple sessions and, after it diminishes in extinction, the alcohol context retains the capacity to augment reinstatement. Systemically administered eticlopride and chemogenetic inhibition of ventral tegmental area (VTA) dopamine neurons reduce CS-triggered alcohol-seeking. Chemogenetically silencing VTA dopamine terminals in the nucleus accumbens (NAc) core reduces CS-triggered alcohol-seeking, irrespective of context, whereas silencing VTA dopamine terminals in the NAc shell selectively reduces the elevation of CS-triggered alcohol-seeking in an alcohol context. This dissociation reveals new roles for divergent mesolimbic dopamine circuits in the control of responding to a discrete cue for alcohol and in the amplification of this behaviour in an alcohol context.

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Section: Discussionsupporting

confidence: 50%

Dissociable mesolimbic dopamine circuits control responding triggered by alcohol-predictive discrete cues and contexts

et al. 2020

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“…Alternative models focus on ethanol seeking behavior as a way to replicate relapse. Similar to other drugs, seeking behavior can be induced by priming injections of ethanol, stress, ethanol-paired cues or a combination of these factors (Le et al, 1998; Liu and Weiss, 2002; LeCocq et al, 2018). Using an alcohol-preferring rat strain, Giuliano et al (2015) developed a different model of cue-induced alcohol-seeking.…”

Section: Models Of Alcohol Intakementioning

confidence: 99%

Understanding Addiction Using Animal Models

Kuhn

Kalivas

Bobadilla

2019

Front. Behav. Neurosci.

129

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Drug addiction is a neuropsychiatric disorder with grave personal consequences that has an extraordinary global economic impact. Despite decades of research, the options available to treat addiction are often ineffective because our rudimentary understanding of drug-induced pathology in brain circuits and synaptic physiology inhibits the rational design of successful therapies. This understanding will arise first from animal models of addiction where experimentation at the level of circuits and molecular biology is possible. We will review the most common preclinical models of addictive behavior and discuss the advantages and disadvantages of each. This includes non-contingent models in which animals are passively exposed to rewarding substances, as well as widely used contingent models such as drug self-administration and relapse. For the latter, we elaborate on the different ways of mimicking craving and relapse, which include using acute stress, drug administration or exposure to cues and contexts previously paired with drug self-administration. We further describe paradigms where drug-taking is challenged by alternative rewards, such as appetitive foods or social interaction. In an attempt to better model the individual vulnerability to drug abuse that characterizes human addiction, the field has also established preclinical paradigms in which drug-induced behaviors are ranked by various criteria of drug use in the presence of negative consequences. Separation of more vulnerable animals according to these criteria, along with other innate predispositions including goal- or sign-tracking, sensation-seeking behavior or impulsivity, has established individual genetic susceptibilities to developing drug addiction and relapse vulnerability. We further examine current models of behavioral addictions such as gambling, a disorder included in the DSM-5, and exercise, mentioned in the DSM-5 but not included yet due to insufficient peer-reviewed evidence. Finally, after reviewing the face validity of the aforementioned models, we consider the most common standardized tests used by pharmaceutical companies to assess the addictive potential of a drug during clinical trials.

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“…To estimate CS port entries independent of baseline exploratory activity, normalised-CS port entries were calculated by subtracting the Pre-CS port entries from the CS port entries (LeCocq et al, 2018; Panayi and Killcross, 2018; Villaruel et al, 2018). Pre-CS port entries were low throughout all phases of each experiment, with means±standard error of the mean (SEM) ranging between 0.67±0.2 and 4.58±1.5 during training and 0±0 and 2.5±0.8 at test.…”

Section: Methodsmentioning

confidence: 99%

“…Ports were checked at the end of each session to ensure that all the alcohol was consumed. The mean ingested alcohol dose during the final session of training ranged from 0.8-1.2 g/kg, which we showed previously resulted in blood alcohol concentrations of 40-60 mg/dL (Cofresí et al, 2018;LeCocq et al, 2018). Inter-trial intervals (which excluded the pre-CS, CS and post-CS intervals) were randomly selected from a list of possible durations with a mean of 240 s (120, 240 or 360 s).…”

Section: Behavioural Trainingmentioning

confidence: 99%

The medial prefrontal cortex is required for responding to alcohol-predictive cues but only in the absence of alcohol delivery

et al. 2019

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The medial prefrontal cortex is required for responding to alcohol-predictive cues but only in the absence of alcohol delivery. Journal of Psychopharmacology. AbstractBackground: The prelimbic medial prefrontal cortex is implicated in promoting drug-seeking in relapse tests. However, drug-seeking behaviour is typically extinguished before a test and tests normally occur without drug delivery. Aims:We investigated the involvement of the prelimbic and the infralimbic cortex in responding elicited by a non-extinguished cue for alcohol that was presented without alcohol in an alcohol-associated context or a neutral context, and in responding to the same cue when it was paired with alcohol. Methods:Male, Long-Evans rats (220-240 g on arrival) were acclimated to 15% ethanol (v/v; 'alcohol') and then trained to associate a conditioned stimulus (10 s white noise; 15 trials/session) with alcohol delivery into a fluid port (0.2 mL/conditioned stimulus, 3 mL per session) for oral intake. Conditioning sessions occurred in a specific 'alcohol context' and were alternated daily with exposure to a second 'neutral' context that contained neither the conditioned stimulus nor alcohol. Results:At test, functional prelimbic cortex inactivation using baclofen/muscimol reduced fluid port entries elicited by a non-extinguished conditioned stimulus that was presented without alcohol, but had no subsequent impact on port entries when the conditioned stimulus was paired with alcohol. Similar results were obtained following infralimbic cortex inactivation; however, infralimbic cortex inactivation also non-specifically reduced port entries in the absence of alcohol. Conclusions:These data indicate that the prelimbic and infralimbic cortex are involved in responding to cues for alcohol

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Modeling Relapse to Pavlovian Alcohol‐Seeking in Rats Using Reinstatement and Spontaneous Recovery Paradigms

Abstract: The reinstatement and spontaneous recovery effects revealed herein provide evidence of viable new behavioral paradigms for testing interventions against relapse.

Cited by 19 publications

References 49 publications

Dissociable mesolimbic dopamine circuits control responding triggered by alcohol-predictive discrete cues and contexts

Dissociable mesolimbic dopamine circuits control responding triggered by alcohol-predictive discrete cues and contexts

Understanding Addiction Using Animal Models

The medial prefrontal cortex is required for responding to alcohol-predictive cues but only in the absence of alcohol delivery

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