Intermittent intake of rapid cocaine injections promotes the risk of relapse and increases mesocorticolimbic BDNF levels during abstinence

Gueye, Aliou B.; Allain, Florence; Samaha, Anne‐Noël

doi:10.1038/s41386-018-0249-8

Cited by 34 publications

(32 citation statements)

References 49 publications

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“…In conclusion, studies utilizing the IntA procedure are more consistent with the view that the pathological motivation to seek and take cocaine in addiction is due, at least in part, to a hyper-responsive dopaminergic state, consistent with an incentive-sensitization view of addiction (Robinson & Berridge, 1993;Berridge & Robinson, 2016). Of course, a syndrome as complex as addiction is not going to be reducible to changes in a single neurotransmitter system, or even a single psychological process, and it remains to be seen what other neuropsychological functions are altered by IntA experience (e.g., Allain et al, 2017;Gueye et al, 2018;James et al, 2018).…”

Section: Discussionmentioning

confidence: 73%

“…These findings establish that IntA, a cocaine selfadministration procedure that is especially effective in producing incentive-sensitization and addiction-like behavior, also sensitizes the dopaminergic response to cocaine. Finally, IntA also has been reported to be especially effective in producing a number of other neurobiological effects related to the development of addiction-like behavior, including dysregulation of mGluR2/3 receptor function (Allain et al, 2017), elevated BDNF levels (Gueye et al, 2018), and increased activity in orexin/hypocretin neurons (James et al, 2018).…”

Section: Inta But Not Lga Sensitizes Cocaine-evoked Dopamine Overflowmentioning

confidence: 99%

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Incentive and dopamine sensitization produced by intermittent but not long access cocaine self-administration

Kawa

Valenta

Kennedy

et al. 2018

Preprint

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242 Manuscript -9002ABSTRACT Recent studies suggest that the temporal pattern of drug use (pharmacokinetics) has a profound effect on the ability of self-administered cocaine to produce addiction-like behavior in rodents, and to change the brain. To further address this issue, we compared the effects of Long Access (LgA) cocaine self-administration, which is widely used to model the transition to addiction, with Intermittent Access (IntA), which is thought to better reflect the pattern of drug use in humans, on the ability of self-administered cocaine to increase dopamine (DA) overflow in the core of the nucleus accumbens (using in vivo microdialysis), and to produce addiction-like behavior. IntA experience was more effective than LgA in producing addiction-like behavior -a drug experience-dependent increase in motivation for cocaine assessed using behavioral economic procedures, and cue-induced reinstatement -despite much less total drug consumption. There were no group differences in basal levels of DA in dialysate, but a single self-administered IV injection of cocaine increased DA in the core of the nucleus accumbens to a greater extent in rats with prior IntA experience than those with LgA or Short Access (ShA) experience, and the latter two groups did not differ. Furthermore, high motivation for cocaine was associated with a high DA response. Thus, IntA, but not LgA, produced both incentive and DA sensitization. This is consistent with the notion that a hyper-responsive dopaminergic system may contribute to the transition from casual patterns of drug use to the problematic patterns that define addiction.

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Section: Discussionmentioning

confidence: 73%

Section: Inta But Not Lga Sensitizes Cocaine-evoked Dopamine Overflowmentioning

confidence: 99%

Incentive and dopamine sensitization produced by intermittent but not long access cocaine self-administration

Kawa

Valenta

Kennedy

et al. 2018

Preprint

View full text Add to dashboard Cite

show abstract

“…In conclusion, studies utilizing the IntA procedure are more consistent with the view that the pathological motivation to seek and take cocaine in addiction is due, at least in part, to a hyper‐ responsive dopaminergic state, consistent with an incentive‐sensitization view of addiction (Berridge & Robinson, ; Robinson & Berridge, ). Of course, a syndrome as complex as addiction is not going to be reducible to changes in a single neurotransmitter system, or even a single psychological process, and it remains to be seen what other neuropsychological functions are altered by IntA experience (e.g., Allain et al., ; Gueye et al., ; James et al., ). Nevertheless, the growing evidence concerning the importance of pharmacokinetic factors in promoting the development of addiction suggests these need to be given greater consideration in preclinical models of addiction (Allain et al., ; Kawa et al., ).…”

Section: Discussionmentioning

confidence: 99%

Incentive and dopamine sensitization produced by intermittent but not long access cocaine self‐administration

Kawa

Valenta

Kennedy

et al. 2019

Eur J of Neuroscience

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The temporal pattern of drug use (pharmacokinetics) has a profound effect on the ability of self‐administered cocaine to produce addiction‐like behavior in rodents, and to change the brain. To further address this issue, we compared the effects of long access (LgA) cocaine self‐administration, which is widely used to model the transition to addiction, with intermittent access (IntA), which is thought to better reflect the pattern of drug use in humans, on the ability of a single, self‐administered injection of cocaine to increase dopamine (DA) overflow in the core of the nucleus accumbens (using in vivo microdialysis), and to produce addiction‐like behavior. IntA experience was more effective than LgA in producing addiction‐like behavior—a drug experience‐dependent increase in motivation for cocaine assessed using behavioral economic procedures, and cue‐induced reinstatement—despite much less total drug consumption. There were no group differences in basal levels of DA in dialysate [DA], but a single self‐administered IV injection of cocaine increased [DA] in the core of the nucleus accumbens to a greater extent in rats with prior IntA experience than those with LgA or limited access experience, and the latter two groups did not differ. Furthermore, high motivation for cocaine was associated with a high [DA] response. Thus, IntA, but not LgA, produced both incentive and DA sensitization. This is consistent with the notion that a hyper‐responsive dopaminergic system may contribute to the transition from casual patterns of drug use to the problematic patterns that define addiction.

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“…Rats taking faster i.v. infusions of cocaine [injected over 5 versus 90 seconds (s)] consume more drug (Allain et al, 2018;Bouayad-Gervais et al, 2014;Minogianis et al, 2013;Wakabayashi et al, 2010), more readily develop psychomotor sensitization (Allain et al, 2017), respond more for cocaine under a PR schedule (Allain et al, 2017;Bouayad-Gervais et al, 2014;Liu et al, 2005;Minogianis et al, 2013), and show enhanced relapse-like behaviour following abstinence (Gueye et al, 2019;Wakabayashi et al, 2010).…”

Section: Introductionmentioning

confidence: 99%

“…LgA rats take much more drug, but IntA rats show more incentive motivation for cocaine, as measured either by behavioural economic indicators or responding for the drug under PR (Algallal et al, 2019;Allain et al, 2018;Kawa et al, 2016;Zimmer et al, 2012). IntA rats also persist in responding for cocaine in spite of an adverse consequence (i.e., mild footshock), they seek the drug when it is not available, and they show stronger cue-induced relapse behaviour than generally seen in LgA-rats (Gueye et al, 2019;Kawa et al, 2016;Nicolas et al, 2019;Singer et al, 2018).…”

Section: Introductionmentioning

confidence: 99%

Taking rapid and intermittent cocaine infusions enhances both incentive motivation for the drug and cocaine-induced gene regulation in corticostriatal regions

Minogianis

Samaha

2020

Preprint

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A goal in addiction research is to distinguish forms of neuroplasticity that are involved in the transition to addiction from those involved in mere drug taking. Animal models of drug selfadministration are essential in this context. Here, we compared in male rats two cocaine selfadministration procedures that differ in the extent to which they evoke addiction-like behaviours. We measured both incentive motivation for cocaine using progressive ratio procedures, and cocaine-induced c-fos mRNA expression, a marker of neuronal activity. Rats self-administered intravenous cocaine (0.25 mg/kg/infusion) for seven daily 6-hour sessions. One group had intermittent access (IntA; 6 minutes ON, 26 minutes OFF x 12) to rapid infusions (delivered over 5 seconds). This models the temporal kinetics of human cocaine use and produces robust addiction-like behaviour. The other group had Long access (LgA) to slower infusions (90 seconds). This produces high levels of intake without promoting robust addiction-like behaviour. LgA-90s rats took twice as much cocaine as IntA-5s rats did, but IntA-5s rats showed greater incentive motivation for the drug. Following a final self-administration session, we quantified cfos mRNA expression in corticostriatal regions. Compared to LgA-90s rats, IntA-5s rats had more cocaine-induced c-fos mRNA in the orbitofrontal and prelimbic cortices and the caudateputamen. Thus, a cocaine self-administration procedure (intermittent intake of rapid infusions) that promotes increased incentive motivation for the drug also enhances cocaine-induced gene regulation in corticostriatal regions. This suggests that increased drug-induced recruitment of these regions could contribute to the neural and behavioural plasticity underlying the transition to addiction.

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Intermittent intake of rapid cocaine injections promotes the risk of relapse and increases mesocorticolimbic BDNF levels during abstinence

Cited by 34 publications

References 49 publications

Incentive and dopamine sensitization produced by intermittent but not long access cocaine self-administration

Incentive and dopamine sensitization produced by intermittent but not long access cocaine self-administration

Incentive and dopamine sensitization produced by intermittent but not long access cocaine self‐administration

Taking rapid and intermittent cocaine infusions enhances both incentive motivation for the drug and cocaine-induced gene regulation in corticostriatal regions

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