Lateral septum stimulation disinhibits dopaminergic neurons in the antero-ventral region of the ventral tegmental area: Role of GABA-A alpha 1 receptors

Vega-Quiroga, Ignacio; Yarur, Héctor E.; Gysling, Katia

doi:10.1016/j.neuropharm.2017.09.034

Cited by 36 publications

(42 citation statements)

References 47 publications

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“…; Vega‐Quiroga et al . ). To test whether diazepam could reverse the effects of LS inhibition on cocaine demand elasticity, we gave animals with stable BE behavior either 2‐mg/kg diazepam or vehicle IP, followed by an intracranial microinjection of B‐M or aCSF into LS 30 minutes later; animals were retested on a BE paradigm immediately after the intracranial injection.…”

Section: Resultsmentioning

confidence: 97%

“…Recently, LS stimulation was found to promote disinhibition of DA neurons via the GABA Aα1 receptor on VTA GABAergic neurons (Vega‐Quiroga et al . ). Our laboratory found that inhibiting LS input to VTA reduces context‐induced reinstatement, indicating that LS disinhibition of VTA DA neurons is an important connection that drives drug seeking (Luo et al .…”

Section: Discussionmentioning

confidence: 97%

“…; Jonsson et al . ; Vega‐Quiroga, Yarur, & Gysling ). Recently, it has been shown that inhibition of GABA Aα1 receptor‐containing VTA GABA neurons is necessary for LS to disinhibit VTA DA neurons (Vega‐Quiroga et al .…”

Section: Introductionmentioning

confidence: 99%

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Lateral septum inhibition reduces motivation for cocaine: Reversal by diazepam

Pantazis

Aston‐Jones

2019

Addiction Biology

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The lateral septum (LS) is a brain region implicated in motivation, addiction, anxiety, and affect. We recently found that LS is necessary for cocaine-seeking behaviors including conditioned place preference and reinstatement of extinguished drug seeking, which involve LS input to limbic regions including ventral tegmental area (VTA) and orexin neurons in hypothalamus. Here, we microinjected baclofen-muscimol (B-M) in LS prior to testing in a behavioral economics (BE) paradigm. We found that intra-LS B-M decreased motivation (increased demand elasticity; α) for cocaine, but did not change consumption at low effort (Q 0 ). We also compared the effects of LS inhibition with the effects of treatment with the benzodiazepine diazepam, which has been shown to facilitate reward pathways and disinhibit VTA dopamine neurons.Pretreatment with diazepam blocked the effects of LS inhibition and restored cocaine demand to that following vehicle treatment. These changes in cocaine demand after LS inhibition or diazepam were not due to effects on anxiety, as both manipulations produced similar effects on anxiety measures but opposing effects on drug taking.Collectively, these studies point to LS as a critical region driving motivation for cocaine, likely through its interactions with the mesolimbic dopamine system.

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Section: Resultsmentioning

confidence: 97%

Section: Discussionmentioning

confidence: 97%

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Lateral septum inhibition reduces motivation for cocaine: Reversal by diazepam

Pantazis

Aston‐Jones

2019

Addiction Biology

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“…Furthermore, blocking CRFR1 increased DA levels in the VTA of rats previously exposed to repeated stress by immobilization (Sotomayor-Zárate et al, 2015). More recently, Vega-Quiroga et al (2018), showed that stimulation of the LS increased DA levels in the VTA by innervating GABAergic interneurons and decreasing GABA-induced inhibition of DA neurons (Vega-Quiroga et al, 2018). Together, these results demonstrate that stress determines DA levels in the LS and VTA in response to cocaine by regulating CRF binding on CRFR1.…”

Section: Contributions From Latin Americamentioning

confidence: 99%

Interaction Between Stress and Addiction: Contributions From Latin-American Neuroscience

et al. 2018

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Drug addiction is a chronic neuropsychiatric disorder that escalates from an initial exposure to drugs of abuse, such as cocaine, cannabis, or heroin, to compulsive drug-seeking and intake, reduced ability to inhibit craving-induced behaviors, and repeated cycles of abstinence and relapse. It is well-known that chronic changes in the brain’s reward system play an important role in the neurobiology of addiction. Notably, environmental factors such as acute or chronic stress affect this system, and increase the risk for drug consumption and relapse. Indeed, the HPA axis, the autonomic nervous system, and the extended amygdala, among other brain stress systems, interact with the brain’s reward circuit involved in addictive behaviors. There has been a growing interest in studying the molecular, cellular, and behavioral mechanisms of stress and addiction in Latin-America over the last decade. Nonetheless, these contributions may not be as strongly acknowledged by the broad scientific audience as studies coming from developed countries. In this review, we compile for the first time a series of studies conducted by Latin American-based neuroscientists, who have devoted their careers to studying the interaction between stress and addiction, from a neurobiological and clinical perspective. Specific contributions about this interaction include the study of CRF receptors in the lateral septum, investigations on the neural mechanisms of cross-sensitization for psychostimulants and ethanol, the identification of the Wnt/β-catenin pathway as a critical neural substrate for stress and addiction, and the emergence of the cannabinoid system as a promising therapeutic target. We highlight animal and human studies, including for instance, reports coming from Latin American laboratories on single nucleotide polymorphisms in stress-related genes and potential biomarkers of vulnerability to addiction, that aim to bridge the knowledge from basic science to clinical research.

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“…[1][2][3] LS is a GABAergic nucleus that projects to ventral tegmental area (VTA) and nucleus accumbens (NAc) making a fine tuning on dopamine (DA) and GABA neurons. 4 Besides, LS GABAergic neurons are under the influence of a basal inhibitory tone of GABAergic neurons from the medial septum and other collateral local GABAergic projections. 5 It has been shown that LS is activated in response to contextual stimuli associated with reward, 6 suggesting that the LS may be a relay station of motivational and contextual information.…”

Section: Introductionmentioning

confidence: 99%

Vasopressin in the lateral septum decreases conditioned place preference to amphetamine and nucleus accumbens dopamine release

et al. 2019

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The lateral septum (LS) is a limbic nucleus interconnected with several brain areas involved in the regulation of mood and reward. Vasopressin (AVP) is a neuropeptide that has been related to the effects of drugs of abuse, but its role in the addictive process is poorly understood. LS expresses a high density of AVP 1A receptors (V 1A). The aim of this work was to examine whether the modulation of LS AVP system affects the behavioral and neurochemical responses to amphetamine (AMPH) in male rats. Our results show that AMPH-induced conditioned place preference (CPP) produces a decrease in LS AVP content. Besides, we demonstrate that the microinjection of AVP in the LS impairs the expression of AMPH-induced CPP and that this effect is mediated by the activation of the V 1A receptor in the LS. AVP microinjection in the LS elicited a decrease in neuronal activity in the nucleus accumbens (NAc) in animals subjected to AMPH conditioning. Finally, AVP microinjection in the LS decreased dopamine (DA) release in the NAc. Overall, our data demonstrate that intra-LS AVP diminishes the expression of AMPH conditioning behavior while decreasing neuronal activity and DA release in the NAc. Presumably, the effects of AVP in the LS produce an inhibition of GABAergic projections to the VTA, increasing local inhibitory tone in this nucleus, which in turn reduces the activity of DA projections to NAc. Thus, these results contribute to the knowledge about the role of AVP in LS in regulating the reward circuit and addictive like behaviors.

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Lateral septum stimulation disinhibits dopaminergic neurons in the antero-ventral region of the ventral tegmental area: Role of GABA-A alpha 1 receptors

Cited by 36 publications

References 47 publications

Lateral septum inhibition reduces motivation for cocaine: Reversal by diazepam

Lateral septum inhibition reduces motivation for cocaine: Reversal by diazepam

Interaction Between Stress and Addiction: Contributions From Latin-American Neuroscience

Vasopressin in the lateral septum decreases conditioned place preference to amphetamine and nucleus accumbens dopamine release

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