Chemogenetic activation of dopamine neurons in the ventral tegmental area, but not substantia nigra, induces hyperactivity in rats

Boekhoudt, Linde; Omrani, Azar; Luijendijk, Mieneke C. M.; Wolterink-Donselaar, Inge G.; Wijbrans, Ellen C.; Plasse, G; Adan, Roger A.H.

doi:10.1016/j.euroneuro.2016.09.003

Cited by 78 publications

(93 citation statements)

References 34 publications

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“…These counts produced an average selectivity of mCherry-expression for TH positive cells of 95.8% and a transfection efficiency of 24.8% ( Fig. 4c), which are comparable to similar measures of selectivity in TH::Cre rats 20,[31][32][33][34][35] . We also observed mCherry expressing TH positive processes in the NAc (Fig.…”

Section: Chemogenetic Targeting Of Vta Dopamine Neurons In Th::cre Rasupporting

confidence: 66%

Divergent mesolimbic dopamine circuits support alcohol-seeking triggered by discrete cues and contexts

Valyear¹,

Glovaci²,

Zaari³

et al. 2018

Preprint

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Discrete and contextual cues that predict alcohol trigger alcohol-seeking. However, the extent to which context influences alcohol-seeking triggered by discrete cues, and the neural mechanisms underlying these responses, are not well known. We show that, relative to a neutral context, a context associated with alcohol persistently elevated alcohol-seeking triggered by a discrete cue, and supported higher levels of priming-induced reinstatement. Alcohol-seeking triggered by a discrete cue in a neutral context was reduced by designer receptor-mediated inhibition of ventral tegmental area (VTA) dopamine neurons in TH::Cre rats. Inhibiting terminals of VTA dopamine neurons in the nucleus accumbens (NAc) core reduced alcohol-seeking triggered by a discrete cue, irrespective of context, whereas inhibiting VTA dopamine terminals in the NAc shell selectively reduced the elevation of alcohol-seeking triggered by a discrete cue in an alcohol context. This dissociation highlights unique roles for divergent mesolimbic dopamine circuits in alcohol-seeking driven by discrete and contextual environmental cues.

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Section: Chemogenetic Targeting Of Vta Dopamine Neurons In Th::cre Rasupporting

confidence: 66%

Divergent mesolimbic dopamine circuits support alcohol-seeking triggered by discrete cues and contexts

Valyear¹,

Glovaci²,

Zaari³

et al. 2018

Preprint

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show abstract

“…These projections include local dopaminergic neurons of the VTA and cholinergic interneurons in the NAc [40] and increased activation of GABA neurons may reduce dopaminergic signaling. Activation of VTA dopaminergic neurons using a DREADD-G q receptor increases locomotor activity in both mice and rats [43,44]. However, we do not observe increased locomotion in our study; hence, there appears to be a functional difference between activating dopaminergic neurons only and activating dopaminergic and GABAergic neurons in the VTA, perhaps due to increased inhibition from GABAergic neurons on dopaminergic neurons.…”

Section: Discussioncontrasting

confidence: 68%

Exploring the Behavioral and Metabolic Phenotype Generated by Re-Introduction of the Ghrelin Receptor in the Ventral Tegmental Area

Skov

Jensen

Christiansen

et al. 2017

IJMS

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Ghrelin receptor (Ghr-R) signaling in neurons of the ventral tegmental area (VTA) can modulate dopaminergic function and the reward-related effects of both palatable foods and drugs of abuse. In this study, we re-introduced the Ghr-R in VTA neurons in Ghr-R knockout mice (Ghr-RVTA mice) to specifically study the importance of the constitutively active Ghr-R for VTA neuronal signaling. Our results showed that re-introduction of the Ghr-R in the VTA had no impact on body weight or food intake under basal conditions. However, during novel environment stress Ghr-RVTA mice showed increased food intake and energy expenditure compared to Ghr-R knockout mice, demonstrating the significance of Ghr-R signaling in the response to stress. Ghr-RVTA mice also showed increased cocaine-induced locomotor activity compared to Ghr-R knockout mice, highlighting the importance of ghrelin signaling for the reward-related effects of activation of VTA neurons. Overall, our data suggest that re-introduction of the Ghr-R in the mesolimbic reward system of Ghr-R knockout mice increases the level of activation induced by both cocaine and novelty stress.

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“…Adaptations in the CPu has been associated with methamphetamine sensitization (Li et al 2016a; Li et al 2016b; Yan et al 2014). However, the subdivisions of the striatum have important functional differences that need to be considered (Boekhoudt et al 2016). Indeed, we have previously shown that the effects of FTAT expression on dopamine levels in the CPu and Acb are opposing in nature (Kesby et al 2016b).…”

Section: Discussionmentioning

confidence: 99%

HIV-1 TAT protein enhances sensitization to methamphetamine by affecting dopaminergic function

Kesby

Najera

Romoli

et al. 2017

Brain, Behavior, and Immunity

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Methamphetamine abuse is common among humans with immunodeficiency virus (HIV). The HIV-1 regulatory protein TAT induces dysfunction of mesolimbic dopaminergic systems which may result in impaired reward processes and contribute to methamphetamine abuse. These studies investigated the impact of TAT expression on methamphetamine-induced locomotor sensitization, underlying changes in dopamine function and adenosine receptors in mesolimbic brain areas and neuroinflammation (microgliosis). Transgenic mice with doxycycline-induced TAT protein expression in the brain were tested for locomotor activity in response to repeated methamphetamine injections and methamphetamine challenge after a 7-day abstinence period. Dopamine function in the nucleus accumbens (Acb) was determined using high performance liquid chromatography. Expression of dopamine and/or adenosine A receptors (ADORA) in the Acb and caudate putamen (CPu) was assessed using RT-PCR and immunohistochemistry analyses. Microarrays with pathway analyses assessed dopamine and adenosine signaling in the CPu. Activity-dependent neurotransmitter switching of a reserve pool of non-dopaminergic neurons to a dopaminergic phenotype in the ventral tegmental area (VTA) was determined by immunohistochemistry and quantified with stereology. TAT expression enhanced methamphetamine-induced sensitization. TAT expression alone decreased striatal dopamine (D1, D2, D4, D5) and ADORA1A receptor expression, while increasing ADORA2A receptors expression. Moreover, TAT expression combined with methamphetamine exposure was associated with increased adenosine A receptors (ADORA1A) expression and increased recruitment of dopamine neurons in the VTA. TAT expression and methamphetamine exposure induced microglia activation with the largest effect after combined exposure. Our findings suggest that dopamine-adenosine receptor interactions and reserve pool neuronal recruitment may represent potential targets to develop new treatments for methamphetamine abuse in individuals with HIV.

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Chemogenetic activation of dopamine neurons in the ventral tegmental area, but not substantia nigra, induces hyperactivity in rats

Cited by 78 publications

References 34 publications

Divergent mesolimbic dopamine circuits support alcohol-seeking triggered by discrete cues and contexts

Divergent mesolimbic dopamine circuits support alcohol-seeking triggered by discrete cues and contexts

Exploring the Behavioral and Metabolic Phenotype Generated by Re-Introduction of the Ghrelin Receptor in the Ventral Tegmental Area

HIV-1 TAT protein enhances sensitization to methamphetamine by affecting dopaminergic function

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