Role of the orbitofrontal cortex and the dorsal striatum in incentive motivation for cocaine

Minogianis, Ellie-Anna; Servonnet, Alice; Filion, M.; Samaha, Anne‐Noël

doi:10.1016/j.bbr.2019.112026

Cited by 16 publications

(25 citation statements)

References 72 publications

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“…Visual and electrophysiological methods were used to identify SPNs (26,39,(49)(50)(51) was bath applied as a NMDA receptor co-agonist. To determine the effects of GlyRα2s on burst activity, low glycine concentrations (30 µM) and 500 µM sarcosine were bath-applied 3 minutes prior and during the experiment.…”

Section: Animalsmentioning

confidence: 99%

Lack of the glycine receptor alpha 2 increases striatal activity and motivated behavior

Devoght

Comhair

Morelli

et al. 2022

Preprint

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Distinct developmental pathologies, including autism spectrum disorder and schizophrenia, exhibit impaired reward-motivated behavior. Key to proper reward-motivated behavior is the integration of dopaminergic and glutamatergic inputs to the striatum. The glycine alpha 2 receptor (GlyRα2) is the single functionally expressed glycine receptor in adult striatum, and is therefore ideally positioned to modulate striatal behavior and cellular signal integration. Here, we report excessive appetitive conditioning in GlyRα2 knockout animals. We next show that depletion of GlyRα2 enhances dopamine-induced increases in the activity of putative dopamine D1-expressing striatal projection neurons, while not affecting dopamine neuron activity. These in vivo behavioral changes are tied to enhanced striatal activation in GlyRα2 KO mice, since we found excessive locomotor responses to amphetamine in GlyRα2 KO mice that correlate with immediate early gene c-fos expression in the dorsal striatum. 3-D modeling revealed activation of cell ensembles in the striatum in response to D-amphetamine, an increase in number of cells but no shift in intercell distance histograms, in agreement with unaltered dopamine release, in GlyRα2 KO mice. Taken together, we show that depletion of GlyRα2 impairs reward-motivated behavior and altered striatal signal integration. This sheds important light onto the cellular mechanisms that underlie reward function, and pave the way towards novel therapeutics for the treatment of e.g. schizophrenia and autism spectrum disorder.

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Section: Animalsmentioning

confidence: 99%

Lack of the glycine receptor alpha 2 increases striatal activity and motivated behavior

Devoght

Comhair

Morelli

et al. 2022

Preprint

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“…Second, substantial monosynaptic glutamatergic inputs connect the OFC to the caudate-putamen (Berendse et al, 1992;Carter, 1982;Gerfen, 1992;McGeorge and Faull, 1989;Schilman et al, 2008), and glutamate from corticostriatal afferents mediates drug-induced c-fos mRNA in the caudate-putamen, particularly when drugs are experienced under conditions that promote sensitization-related changes in brain and behaviour (Ferguson et al, 2003;Ferguson and Robinson, 2004;Snyder-Keller, 1991). Third, recent findings show that in IntA-5s rats, transiently disconnecting the OFC and the caudate-putamen with GABA receptor agonists suppresses incentive motivation to take cocaine (Minogianis et al, 2019), as measured by responding for the drug under a PR schedule of reinforcement. Together, the findings suggest that the roles of the OFC, caudate-putamen and their connections in incentive motivation to take cocaine should be examined further, using circuit-specific chemogenetic or optogenetic manipulations for example.…”

Section: The Mode Of Past Cocaine Use Produces Both Qualitative and Qmentioning

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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“…Clinical studies in substance users found that the OFC dysfunction leads to impaired motives for general rewards but an increased motivation for addictive drugs which gradually develops into a pathological substance craving (28). In addition, inhibition of the OFC or disruption of the OFC-BLA connectivity reduces contextor cue-induced drug seeking (28)(29)(30)(31). Although the current evidence supports an idea that the OFC intervention has an immediate effect on cue-induced craving, there is no report on whether inhibition of the OFC can produce a sustained effect to reduce drug-seeking.…”

Section: Introductionmentioning

confidence: 99%

“…In specific, we will use theta-burst stimulation (TBS), a new pattern of TMS, to modulate the activity in the OFC because of its advantage for stronger effects with shorter duration compared to conventional repetitive TMS ( 40 ). We will choose continuous TBS (cTBS) due to its promised effect on depression of cortical excitability ( 22 , 31 , 33 ). It has been delivered to the medial prefrontal cortex to decrease reactivity to alcohol-related cues and reduce drinking behavior in a recent studies ( 39 ).…”

Section: Introductionmentioning

confidence: 99%

Theta-Burst Stimulation Combined With Virtual-Reality Reconsolidation Intervention for Methamphetamine Use Disorder: Study Protocol for a Randomized-Controlled Trial

Wen

Hao²,

Chen³

et al. 2022

Front. Psychiatry

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BackgroundCraving associated with drug-related memory is one of the key factors that induce the relapse of methamphetamine (MA). Disruption or modulation of the reconsolidation of drug-related memory may serve as an option for clinical treatment of MA addiction. This protocol proposes to use virtual reality (VR) to retrieve drug-associated memory and then use transcranial magnetic stimulation (TMS) at the neural circuit that encodes the reward value of drug cues to provide a non-invasive intervention during reconsolidation. We aim to evaluate the effectiveness of TMS treatment after VR retrieval on the reduction of cue reactivity and craving of MA.MethodsThis is a randomized, double-blind, sham-controlled, parallel group trial, targeting participants with MA use disorder aged from 18 to 45 years old. Forty-five eligible volunteers in Shanxi Drug Rehabilitation Center will be recruited and be randomly allocated into three parallel groups, receiving either 1) MA-related cues retrieval in VR combined with active TMS (MA VR scene + TBS) or 2) sham TMS (MA VR scene + sham TBS), or 3) neutral cues retrieval in VR combined with active TMS (neutral VR scene + TBS). Two sessions of post-VR-retrieval TBS will be scheduled on two separate days within 1 week. The primary outcome will detect the memory-related activity by the electroencephalography (EEG) reactivity to drug cues in VR scenes. Secondary outcomes are the self-reported MA craving in VR scene, the physiological parameter (cue-induced heart rate) and the scores of psychological questionnaires including anxiety, depression, and mood. All primary and secondary outcomes will be assessed at baseline, 1-week, and 1-month post-intervention. Assessments will be compared between the groups of 1) MA VR scene + TBS, 2) MA VR scene + sham TBS and 3) neutral VR scene + TBS.DiscussionThis will be the first study to examine whether the TMS modulation after VR retrieval can reduce self-reported craving and drug-related cue reactivity. It will promote the understanding of the neural circuit mechanism of the reconsolidation-based intervention and provide an effective treatment for MA use disorder patients.Clinical Trial Registration[Chinese Clinical Trial Registry], identifier [ChiCTR1900026902]. Registered on 26 October 2019.

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Role of the orbitofrontal cortex and the dorsal striatum in incentive motivation for cocaine

Cited by 16 publications

References 72 publications

Lack of the glycine receptor alpha 2 increases striatal activity and motivated behavior

Lack of the glycine receptor alpha 2 increases striatal activity and motivated behavior

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

Theta-Burst Stimulation Combined With Virtual-Reality Reconsolidation Intervention for Methamphetamine Use Disorder: Study Protocol for a Randomized-Controlled Trial

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