Dataset Information

Astrocytic Mechanisms Involving Kynurenic Acid Control ?9-Tetrahydrocannabinol-Induced Increases in Glutamate Release in Brain Reward-Processing Areas.

ABSTRACT: The reinforcing effects of ?9-tetrahydrocannabinol (THC) in rats and monkeys, and the reinforcement-related dopamine-releasing effects of THC in rats, can be attenuated by increasing endogenous levels of kynurenic acid (KYNA) through systemic administration of the kynurenine 3-monooxygenase inhibitor, Ro 61-8048. KYNA is a negative allosteric modulator of ?7 nicotinic acetylcholine receptors (?7nAChRs) and is synthesized and released by astroglia, which express functional ?7nAChRs and cannabinoid CB1 receptors (CB1Rs). Here, we tested whether these presumed KYNA autoreceptors (?7nAChRs) and CB1Rs regulate glutamate release. We used in vivo microdialysis and electrophysiology in rats, RNAscope in situ hybridization in brain slices, and primary culture of rat cortical astrocytes. Acute systemic administration of THC increased extracellular levels of glutamate in the nucleus accumbens shell (NAcS), ventral tegmental area (VTA), and medial prefrontal cortex (mPFC). THC also reduced extracellular levels of KYNA in the NAcS. These THC effects were prevented by administration of Ro 61-8048 or the CB1R antagonist, rimonabant. THC increased the firing activity of glutamatergic pyramidal neurons projecting from the mPFC to the NAcS or to the VTA in vivo. These effects were averted by pretreatment with Ro 61-8048. In vitro, THC elicited glutamate release from cortical astrocytes (on which we demonstrated co-localization of the CB1Rs and ?7nAChR mRNAs), and this effect was prevented by KYNA and rimonabant. These results suggest a key role of astrocytes in interactions between the endocannabinoid system, kynurenine pathway, and glutamatergic neurotransmission, with ramifications for the pathophysiology and treatment of psychiatric and neurodegenerative diseases.

SUBMITTER: Secci ME

PROVIDER: S-EPMC6393222 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature

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Astrocytic Mechanisms Involving Kynurenic Acid Control Δ<sup>9</sup>-Tetrahydrocannabinol-Induced Increases in Glutamate Release in Brain Reward-Processing Areas.

Secci Maria E ME Mascia Paola P Sagheddu Claudia C Beggiato Sarah S Melis Miriam M Borelli Andrea C AC Tomasini Maria C MC Panlilio Leigh V LV Schindler Charles W CW Tanda Gianluigi G Ferré Sergi S Bradberry Charles W CW Ferraro Luca L Pistis Marco M Goldberg Steven R SR Schwarcz Robert R Justinova Zuzana Z

Molecular neurobiology 20180827 5

The reinforcing effects of Δ<sup>9</sup>-tetrahydrocannabinol (THC) in rats and monkeys, and the reinforcement-related dopamine-releasing effects of THC in rats, can be attenuated by increasing endogenous levels of kynurenic acid (KYNA) through systemic administration of the kynurenine 3-monooxygenase inhibitor, Ro 61-8048. KYNA is a negative allosteric modulator of α7 nicotinic acetylcholine receptors (α7nAChRs) and is synthesized and released by astroglia, which express functional α7nAChRs and ...[more]

PMID: 30151725

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Project description:A food's reward value is dependent on its caloric content. Furthermore, a food's acute reward value also depends on hunger state. The drive to obtain rewards (reward sensitivity), however, differs between individuals. Here, we assessed the association between brain responses to calories in the mouth and trait reward sensitivity in different hunger states. Firstly, we assessed this in data from a functional neuroimaging study (van Rijn et al., 2015), in which participants (n = 30) tasted simple solutions of a non-caloric sweetener with or without a non-sweet carbohydrate (maltodextrin) during hunger and satiety. Secondly, we expanded these analyses to regular drinks by assessing the same relationship in data from a study in which soft drinks sweetened with either sucrose or a non-caloric sweetener were administered during hunger (n = 18) (Griffioen-Roose et al., 2013). First, taste activation by the non-caloric solution/soft drink was subtracted from that by the caloric solution/soft drink to eliminate sweetness effects and retain activation induced by calories. Subsequently, this difference in taste activation was correlated with reward sensitivity as measured with the BAS drive subscale of the Behavioral Activation System (BAS) questionnaire. When participants were hungry and tasted calories from the simple solution, brain activation in the right ventral striatum (caudate), right amygdala and anterior cingulate cortex (bilaterally) correlated negatively with BAS drive scores. In contrast, when participants were satiated, taste responses correlated positively with BAS drive scores in the left caudate. These results were not replicated for soft drinks. Thus, neural responses to oral calories from maltodextrin were modulated by reward sensitivity in reward-related brain areas. This was not the case for sucrose. This may be due to the direct detection of maltodextrin, but not sucrose in the oral cavity. Also, in a familiar beverage, detection of calories per se may be overruled by a conditioned response to its flavor. In conclusion, the brain reward response to calories from a long chain starch sugar (maltodextrin) varies with trait reward sensitivity. The absence of this effect in a familiar beverage warrants further research into its relevance for real life ingestive behavior.

Dataset Information

Astrocytic Mechanisms Involving Kynurenic Acid Control ?9-Tetrahydrocannabinol-Induced Increases in Glutamate Release in Brain Reward-Processing Areas.

Publications

Astrocytic Mechanisms Involving Kynurenic Acid Control Δ<sup>9</sup>-Tetrahydrocannabinol-Induced Increases in Glutamate Release in Brain Reward-Processing Areas.

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