Endocannabinoids Shape Accumbal Encoding of Cue-Motivated Behavior via CB1 Receptor Activation in the Ventral Tegmentum

Oleson, Erik B.; Beckert, Michael; Morra, Joshua T.; Lansink, Carien S.; Cachope, Roger; Abdullah, Rehab A.; Loriaux, Amy L.; Schetters, Dustin; Pattij, Tommy; Roitman, Mitchell F.; Lichtman, Aron H.; Cheer, Joseph F.

doi:10.1016/j.neuron.2011.11.018

Cited by 144 publications

(200 citation statements)

References 67 publications

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“…We previously demonstrated that the endocannabinoid 2-arachidonoylglycerol, but not anandamide, facilitates dopamine release and cue-motivated behavior (Oleson et al, 2012). In the present study, we replicated this distinction by showing that increased 2-arachidonoylglycerol, but not anandamide, concentrations are sufficient to accelerate the temporal response pattern and induced a negative curvature index in a manner similar to WIN 55 212-2.…”

Section: Discussionsupporting

confidence: 83%

“…Our endocannabinoid data suggest that ongoing tone might be required to modulate the incentive to forage, while increased concentrations of 2-arachidonoylglycerol might promote the incentive to obtain the primary food source. On the basis of previous data (Melis et al, 2004;Oleson et al, 2012), we speculate that in the latter case, high-frequency firing of dopamine neurons would increase the on-demand synthesis of 2-arachidonoylglycerol, which would then function to amplify dopamine release and ultimately motivate behavior aimed at obtaining the primary food source.…”

Section: Discussionmentioning

confidence: 76%

“…We began by pharmacologically increasing the two best-characterized endocannabinoids, 2-arachidonoylglycerol and anandamide by antagonizing their respective degradative enzymes, monoacylglycerol lipase (MAGL) and fatty acid amide hydrolase (FAAH) (Cravatt et al, 1996;Fegley et al, 2005;Long et al, 2008). JZL184 is a known MAGL inhibitor (Long et al, 2008), previously shown to increase 2-arachidonoylglycerol in the ventral tegmental area and augment cue-evoked dopamine concentrations while animals behave in cued operant tasks (Oleson et al, 2012). During FI responding, elevating 2-arachidonoylglycerol levels significantly modified the temporal response in a manner resembling WIN 55 212-2 (n ¼ 7; Figure 5c; F (6,27) ¼ 4.763; p ¼ 0.013), with 18 mg/kg (p ¼ 0.01) and 30 mg/kg (po0.01) doses producing a negative curvature index in comparison to vehicle.…”

Section: Resultsmentioning

confidence: 99%

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Cannabinoid Receptor Activation Shifts Temporally Engendered Patterns of Dopamine Release

Oleson

Cachope

Fitoussi

et al. 2013

Neuropsychopharmacol

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The ability to discern temporally pertinent environmental events is essential for the generation of adaptive behavior in conventional tasks, and our overall survival. Cannabinoids are thought to disrupt temporally controlled behaviors by interfering with dedicated brain timing networks. Cannabinoids also increase dopamine release within the mesolimbic system, a neural pathway generally implicated in timing behavior. Timing can be assessed using fixed-interval (FI) schedules, which reinforce behavior on the basis of time. To date, it remains unknown how cannabinoids modulate dopamine release when responding under FI conditions, and for that matter, how subsecond dopamine release is related to time in these tasks. In the present study, we hypothesized that cannabinoids would accelerate timing behavior in an FI task while concurrently augmenting a temporally relevant pattern of dopamine release. To assess this possibility, we measured subsecond dopamine concentrations in the nucleus accumbens while mice responded for food under the influence of the cannabinoid agonist WIN 55 212-2 in an FI task. Our data reveal that accumbal dopamine concentrations decrease proportionally to interval duration-suggesting that dopamine encodes time in FI tasks. We further demonstrate that WIN 55 212-2 dose-dependently increases dopamine release and accelerates a temporal behavioral response pattern in a CB1 receptor-dependent manner-suggesting that cannabinoid receptor activation modifies timing behavior, in part, by augmenting time-engendered patterns of dopamine release. Additional investigation uncovered a specific role for endogenous cannabinoid tone in timing behavior, as elevations in 2-arachidonoylglycerol, but not anandamide, significantly accelerated the temporal response pattern in a manner akin to WIN 55 212-2.

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Section: Discussionsupporting

confidence: 83%

Section: Discussionmentioning

confidence: 76%

Section: Resultsmentioning

confidence: 99%

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Cannabinoid Receptor Activation Shifts Temporally Engendered Patterns of Dopamine Release

Oleson

Cachope

Fitoussi

et al. 2013

Neuropsychopharmacol

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“…Moreover, increased 2-AG signaling in the VTA potentiates cue-evoked increases in the NAc DA and associated reward-seeking (Oleson et al, 2012), and this may participate in the well-known enhancement of cue conditioning that contributes to nicotine reward (Caggiula et al, 2002;Chaudhri et al, 2006). Nicotine-induced elevations in VTA 2-AG were enhanced following repeated drug exposure, and no differences were evident in the 2-AG response to nicotine SA vs YA.…”

Section: Discussionmentioning

confidence: 95%

The Volitional Nature of Nicotine Exposure Alters Anandamide and Oleoylethanolamide Levels in the Ventral Tegmental Area

Buczynski

Polis

Parsons

2012

Neuropsychopharmacol

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Cannabinoid-1 receptors (CB 1 ) have an important role in nicotine reward and their function is disrupted by chronic nicotine exposure, suggesting nicotine-induced alterations in endocannabinoid (eCB) signaling. However, the effects of nicotine on brain eCB levels have not been rigorously evaluated. Volitional intake of nicotine produces physiological and behavioral effects distinct from forced drug administration, although the mechanisms underlying these effects are not known. This study compared the effects of volitional nicotine self-administration (SA) and forced nicotine exposure (yoked administration (YA)) on levels of eCBs and related neuroactive lipids in the ventral tegmental area (VTA) and other brain regions. Brain lipid levels were indexed both by in vivo microdialysis in the VTA and lipid extractions from brain tissues. Nicotine SA, but not YA, reduced baseline VTA dialysate oleoylethanolamide (OEA) levels relative to nicotine-naïve controls, and increased anandamide (AEA) release during nicotine intake. In contrast, all nicotine exposure paradigms increased VTA dialysate 2-arachidonoyl glycerol (2-AG) levels. Thus, nicotine differentially modulates brain lipid (2-AG, AEA, and OEA) signaling, and these modulations are influenced by the volitional nature of the drug exposure. Corresponding bulk tissue analysis failed to identify these lipid changes. Nicotine exposure had no effect on fatty acid amide hydrolase activity in the VTA, suggesting that changes in AEA and OEA signaling result from alterations in their nicotine-induced biosynthesis. Both CB 1 (by AEA and 2-AG) and non-CB 1 (by OEA) targets can alter the excitability and activity of the dopaminergic neurons in the VTA. Collectively, these findings implicate disrupted lipid signaling in the motivational effects of nicotine.

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“…Sub-second changes in DA levels within target regions such as the NAcc are important in reward processing [78,79], and VTA DA stimulation is sufficient to drive intracranial self-stimulation (ICSS) [80,81]. ICSS is also accompanied by increased endocannabinoids that act via CB1 receptors whose blockade reduces the behaviour itself [82,83].…”

Section: Overview (A) Endocannabinoid Role In Dopaminedependent Behavmentioning

confidence: 99%

Hub and switches: endocannabinoid signalling in midbrain dopamine neurons

Melis

Pistis

2012

Phil. Trans. R. Soc. B

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The last decade has provided a wealth of experimental data on the role played by lipids belonging to the endocannabinoid family in several facets of physiopathology of dopamine neurons. We currently suggest that these molecules, being intimately connected with diverse metabolic and signalling pathways, might differently affect various functions of dopamine neurons through activation not only of surface receptors, but also of nuclear receptors. It is now emerging how dopamine neurons can regulate their constituent biomolecules to compensate for changes in either internal functions or external conditions. Consequently, dopamine neurons use these lipid molecules as metabolic and homeostatic signal detectors, which can dynamically impact cell function and fitness. Because dysfunctions of the dopamine system underlie diverse neuropsychiatric disorders, including schizophrenia and drug addiction, the importance of better understanding the correlation between an unbalanced endocannabinoid signal and the dopamine system is even greater. Particularly, because dopamine neurons are critical in controlling incentive-motivated behaviours, the involvement of endocannabinoid molecules in fine-tuning dopamine cell activity opened new avenues in both understanding and treating drug addiction. Here, we review recent advances that have shed new light on the understanding of differential roles of endocannabinoids and their cognate molecules in the regulation of the reward circuit, and discuss their anti-addicting properties, particularly with a focus on their potential engagement in the prevention of relapse.

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Endocannabinoids Shape Accumbal Encoding of Cue-Motivated Behavior via CB1 Receptor Activation in the Ventral Tegmentum

Cited by 144 publications

References 67 publications

Cannabinoid Receptor Activation Shifts Temporally Engendered Patterns of Dopamine Release

Cannabinoid Receptor Activation Shifts Temporally Engendered Patterns of Dopamine Release

The Volitional Nature of Nicotine Exposure Alters Anandamide and Oleoylethanolamide Levels in the Ventral Tegmental Area

Hub and switches: endocannabinoid signalling in midbrain dopamine neurons

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