Cannabinoid Transmission in the Hippocampus Activates Nucleus Accumbens Neurons and Modulates Reward and Aversion-Related Emotional Salience

Loureiro, Michaël; Kramar, Cecilia P.; Renard, Justine; Rosen, Laura G.; Laviolette, Steven R.

doi:10.1016/j.biopsych.2015.10.016

Cited by 42 publications

(36 citation statements)

References 43 publications

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“…Because increased VTA activity in the PCP model might partially derive from downstream effects of higher vHipp influence (i.e., abnormal disinhibition from the NAc-VP system), augmenting the cannabinoid drive onto VP GABAergic neurons could be a therapeutic strategy against vHipp-related hyperdopaminergia, and therefore schizophrenia (Lodge and Grace, 2007; Aguilar et al, 2014). These results are consistent with Loureiro et al (2015, 2016), according to which vHipp CB 1 agonism during urethane anesthesia increases the average neural activity in VTA and NAc shell. Thus, both the PCP model and intra-hippocampal CB 1 receptor activation have been shown to disarrange the NAc-VP-VTA processing, which seems to be treatable with anandamide up-regulation in the VP (Figure 2B).…”

Section: The Ecb System In Schizophrenia: Electrophysiological Findinsupporting

confidence: 93%

“…Green and blue neurons are glutamatergic and dopaminergic, respectively. (B) Studies on: (1) CB 1 receptor activation in vHipp (Loureiro et al, 2015, 2016); (2) downstream consequences of vHipp hyperactivity (i.e., abnormal NAc-VP-VTA disinhibition) induced by the chronic PCP model of schizophrenia, and ameliorating effects of anandamide upregulation through FAAH inhibition (URB-597) (Aguilar et al, 2014); and (3) URB-597 effects on mPFC firing in PCP-treated rats (Aguilar et al, 2016). Red neurons are GABAergic.…”

Section: The Ecb System In Schizophrenia: Electrophysiological Findinmentioning

confidence: 99%

“…(1) Most of the electrophysiological recordings (13 of 23) have been performed in anesthetized rodents, either accompanied (Laviolette and Grace, 2006; Draycott et al, 2014; Gomes et al, 2015; Loureiro et al, 2015, 2016; Renard et al, 2016) or not (Melis et al, 2004a; Dissanayake et al, 2008; Hajós et al, 2008; Raver et al, 2013; Aguilar et al, 2014; Cass et al, 2014; Smucny et al, 2014) by behavioral testing. (2) Some in vitro studies have also included separate behavioral experiments (Jew et al, 2013; Raver et al, 2013; Lovelace et al, 2014, 2015), but most of them have been purely electrophysiological, either accompanied or not by anesthetized recordings (Melis et al, 2004a; Lafourcade et al, 2007; Du et al, 2013; Cass et al, 2014; Raver and Keller, 2014; Kim and Li, 2015; Li and Kim, 2016).…”

Section: The Ecb System In Schizophrenia: Electrophysiological Findinmentioning

confidence: 99%

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Cannabinoids and Vanilloids in Schizophrenia: Neurophysiological Evidence and Directions for Basic Research

et al. 2017

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Much of our knowledge of the endocannabinoid system in schizophrenia comes from behavioral measures in rodents, like prepulse inhibition of the acoustic startle and open-field locomotion, which are commonly used along with neurochemical approaches or drug challenge designs. Such methods continue to map fundamental mechanisms of sensorimotor gating, hyperlocomotion, social interaction, and underlying monoaminergic, glutamatergic, and GABAergic disturbances. These strategies will require, however, a greater use of neurophysiological tools to better inform clinical research. In this sense, electrophysiology and viral vector-based circuit dissection, like optogenetics, can further elucidate how exogenous cannabinoids worsen (e.g., tetrahydrocannabinol, THC) or ameliorate (e.g., cannabidiol, CBD) schizophrenia symptoms, like hallucinations, delusions, and cognitive deficits. Also, recent studies point to a complex endocannabinoid-endovanilloid interplay, including the influence of anandamide (endogenous CB1 and TRPV1 agonist) on cognitive variables, such as aversive memory extinction. In fact, growing interest has been devoted to TRPV1 receptors as promising therapeutic targets. Here, these issues are reviewed with an emphasis on the neurophysiological evidence. First, we contextualize imaging and electrographic findings in humans. Then, we present a comprehensive review on rodent electrophysiology. Finally, we discuss how basic research will benefit from further combining psychopharmacological and neurophysiological tools.

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Section: The Ecb System In Schizophrenia: Electrophysiological Findinsupporting

confidence: 93%

Section: The Ecb System In Schizophrenia: Electrophysiological Findinmentioning

confidence: 99%

Section: The Ecb System In Schizophrenia: Electrophysiological Findinmentioning

confidence: 99%

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Cannabinoids and Vanilloids in Schizophrenia: Neurophysiological Evidence and Directions for Basic Research

et al. 2017

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“…We have reported previously that cannabinoid receptor activation in neural regions extrinsic to the mesolimbic DA pathway, including the NASh, PFC and ventral hippocampus, can strongly modulate both emotional memory salience by increasing VTA DAergic neuronal activity states (Draycott et al., ; Loureiro, Kramar, Renard, Rosen, & Laviolette, ; Loureiro, Renard, Zunder, & Laviolette, ; Norris et al., ). Thus, given our findings that intra‐NASh THC administration strongly potentiated normally nonsalient fear memory formation, we next examined if intra‐NASh THC may similarly modulate DAergic neuronal activity states directly in the VTA, using single‐unit, extracellular neuronal recordings combined with intra‐NASh microinfusions of THC and/or FLU (see methods).…”

Section: Resultsmentioning

confidence: 99%

Delta‐9‐tetrahydrocannabinol potentiates fear memory salience through functional modulation of mesolimbic dopaminergic activity states

Fitoussi

Zunder

Tan

et al. 2018

Eur J of Neuroscience

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Chronic or acute exposure to delta-9-tetrahydrocannabinol (THC), the main psychoactive compound in cannabis, has been associated with numerous neuropsychiatric side-effects, including dysregulation of emotional processing and associative memory formation. Clinical and preclinical evidence suggests that the effects of THC are due to the ability to modulate mesolimbic dopamine (DA) activity states in the nucleus accumbens (NAc) and ventral tegmental area (VTA). Nevertheless, the mechanisms by which THC modulates mesolimbic DA function and emotional processing are not well understood. Using an olfactory associative fear memory procedure combined with in vivo neuronal electrophysiology, we examined the effects of direct THC microinfusions targeting the shell region of the NAc (NASh) and examined how THC may modulate the processing of fear-related emotional memory and concomitant activity states of the mesolimbic DA system. We report that intra-NASh THC dose-dependently potentiates the emotional salience of normally subthreshold fear conditioning cues. These effects were dependent upon intra-VTA transmission through GABAergic receptor mechanisms and intra-NASh DAergic transmission. Furthermore, doses of intra-NASh THC that potentiated fear memory salience were found to modulate intra-VTA neuronal network activity by increasing the spontaneous firing and bursting frequency of DAergic neurones whilst decreasing the activity levels of a subpopulation of putative GABAergic VTA neurones. These findings demonstrate that THC can act directly in the NASh to modulate mesolimbic activity states and induce disturbances in emotional salience and memory formation through modulation of VTA DAergic transmission.

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“…At the neuronal level, many different neurotransmitters modulate social behaviour, either facilitating or inhibiting social interactions. Remarkably, most of the former are well‐known key players of the reward system, such as dopamine, noradrenaline, cannabinoids, oxytocin or opioids (Dolen et al , ; Coria‐Avila et al , ; Baribeau and Anagnostou, ; Loureiro et al , ; Vanderschuren et al , ), and have been initially identified as neurochemical mediators of the motivational/rewarding properties of drugs of abuse and/or as pain killers. In contrast, neurobiological substrates of social avoidance [social avoidance systems (SAS)] have been characterized as main factors of the pain, aggression or stress systems and include 5‐HT, glucocorticoids and neuropeptides such as corticotropin‐releasing factor, arginine vasopressin, substance P or cholecystokinin (Katsouni et al , ; Takahashi et al , ; Barik et al , ; Katsouni et al , ; Gobbroge et al , ).…”

Section: Social Reward and Social Pain: Overlapping Neurobiological Smentioning

confidence: 99%

μ opioid receptor, social behaviour and autism spectrum disorder: reward matters

Pellissier

Gandía

Laboute

et al. 2017

British J Pharmacology

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The endogenous opioid system is well known to relieve pain and underpin the rewarding properties of most drugs of abuse. Among opioid receptors, the μ receptor mediates most of the analgesic and rewarding properties of opioids. Based on striking similarities between social distress, physical pain and opiate withdrawal, μ receptors have been proposed to play a critical role in modulating social behaviour in humans and animals. This review summarizes experimental data demonstrating such role and proposes a novel model, the μ opioid receptor balance model, to account for the contribution of μ receptors to the subtle regulation of social behaviour. Interestingly, μ receptor null mice show behavioural deficits similar to those observed in patients with autism spectrum disorder (ASD), including severe impairment in social interactions. Therefore, after a brief summary of recent evidence for blunted (social) reward processes in subjects with ASD, we review here arguments for altered μ receptor function in this pathology. This article is part of a themed section on Emerging Areas of Opioid Pharmacology. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v175.14/issuetoc.

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Cannabinoid Transmission in the Hippocampus Activates Nucleus Accumbens Neurons and Modulates Reward and Aversion-Related Emotional Salience

Cited by 42 publications

References 43 publications

Cannabinoids and Vanilloids in Schizophrenia: Neurophysiological Evidence and Directions for Basic Research

Cannabinoids and Vanilloids in Schizophrenia: Neurophysiological Evidence and Directions for Basic Research

Delta‐9‐tetrahydrocannabinol potentiates fear memory salience through functional modulation of mesolimbic dopaminergic activity states

μ opioid receptor, social behaviour and autism spectrum disorder: reward matters

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