scholarly journals Alterations in Rat Accumbens Dopamine, Endocannabinoids and GABA Content During WIN55,212-2 Treatment: The Role of Ghrelin

2020 ◽  
Vol 22 (1) ◽  
pp. 210
Author(s):  
Chrysostomos Charalambous ◽  
Marek Lapka ◽  
Tereza Havlickova ◽  
Kamila Syslova ◽  
Magdalena Sustkova-Fiserova

The endocannabinoid/CB1R system as well as the central ghrelin signalling with its growth hormone secretagogoue receptors (GHS-R1A) are importantly involved in food intake and reward/reinforcement processing and show distinct overlaps in distribution within the relevant brain regions including the hypothalamus (food intake), the ventral tegmental area (VTA) and the nucleus accumbens (NAC) (reward/reinforcement). The significant mutual interaction between these systems in food intake has been documented; however, the possible role of ghrelin/GHS-R1A in the cannabinoid reinforcement effects and addiction remain unclear. Therefore, the principal aim of the present study was to investigate whether pretreatment with GHS-R1A antagonist/JMV2959 could reduce the CB1R agonist/WIN55,212-2–induced dopamine efflux in the nucleus accumbens shell (NACSh), which is considered a crucial trigger impulse of the addiction process. The synthetic aminoalklylindol cannabinoid WIN55,212-2 administration into the posterior VTA induced significant accumbens dopamine release, which was significantly reduced by the 3 mg/kg i.p. JMV2959 pretreatment. Simultaneously, the cannabinoid-increased accumbens dopamine metabolic turnover was significantly augmented by the JMV2959 pretreament. The intracerebral WIN55,212-2 administration also increased the endocannabinoid arachidonoylethanolamide/anandamide and the 2-arachidonoylglycerol/2-AG extracellular levels in the NACSh, which was moderately but significantly attenuated by the JMV2959 pretreatment. Moreover, the cannabinoid-induced decrease in accumbens γ-aminobutyric acid/gamma-aminobutyric acid levels was reversed by the JMV2959 pretreatment. The behavioural study in the LABORAS cage showed that 3 mg/kg JMV2959 pretreatment also significantly reduced the systemic WIN55,212-2-induced behavioural stimulation. Our results demonstrate that the ghrelin/GHS-R1A system significantly participates in the rewarding/reinforcing effects of the cannabinoid/CB1 agonist that are involved in cannabinoid addiction processing.

1996 ◽  
Vol 271 (2) ◽  
pp. R388-R392 ◽  
Author(s):  
S. E. Specter ◽  
B. A. Horwitz ◽  
J. L. Beverly

The diminished sensitivity of genetically obese (fa/ fa) Zucker rats to the glucoprivic agent 2-deoxy-D-glucose (2-DG) may involve impaired release of the neurotransmitter gamma-aminobutyric acid (GABA) in discrete regions of the hypothalamus. Extracellular GABA concentrations in the medial (MH) and lateral (LH) hypothalamus of lean (Fa/Fa) and age-matched obese (fa/fa) male Zucker rats before and after 2-DG (1.2 mmol/kg i.v.). Basal GABA concentrations were higher (P < 0.05) in the MH of obese vs. lean rats. No differences were noted in LH GABA levels between lean and obese rats or in baseline extracellular GABA levels between brain regions in lean rats. In lean rats, a characteristic bimodal increase in GABA concentrations was apparent in the MH, whereas GABA concentrations decreased in the LH during the 60 min after 2-DG. No changes in GABA concentrations in dialysate from the MH or LH of obese rats were observed after 2-DG. The alterations in basal activity and responsiveness to glucoprivic stimuli by GABAergic system in the MH of obese rats may reflect a defect in central glucostatic control of food intake and, ultimately, in the hypothesized autonomic imbalance in fa/fa Zucker rat.


1994 ◽  
Vol 11 (5) ◽  
pp. 1003-1012 ◽  
Author(s):  
Jeffrey H. Boatright ◽  
Nara M. Rubim ◽  
P. Michael Iuvone

AbstractEndogenous dopamine release in the retina of the African clawed frog (Xenopus laevis) increases in light and decreases in darkness. The roles of the inhibitory amino acid transmitters gamma-aminobutyric acid (GABA) and glycine in regulating this light/dark difference in dopamine release were explored in the present study. Exogenous GABA, the GABA-A receptor agonist muscimol, the GABA-B receptor agonist baclofen, and the GABA-C receptor agonist cis-aminocrotonic acid (CACA) suppressed light-evoked dopamine overflow from eyecups. The effects of GABA-A and -B receptor agonists were selectively reversed by their respective receptor-specific antagonists, whereas the effect of CACA was reversed by the competitive GABA-A receptor antagonist bicuculline. The benzodiazepine diazepam enhanced the effect of muscimol on light-evoked dopamine release. Both GABA-A and -B receptor antagonists stimulated dopamine release in light or darkness. Bicuculline was more potent in light than in darkness. These data suggest that retinal dopaminergic neurons are inhibited by GABA-A and -B receptor activation in both light and darkness but that GABA-mediated inhibitory tone may be greater in darkness than in light.Exogenous glycine inhibited light-stimulated dopamine release in a concentration-dependent and strychnine-sensitive manner. However, strychnine alone did not increase dopamine release in light or darkness, nor did it augment bicuculline-stimulated release in darkness. Additionally, both strychnine and 7-chlorokynurenate, an antagonist of the strychnine-insensitive glycine-binding site of the N-methyl-D-aspartate subtype of glutamate receptor, suppressed light-evoked dopamine release. Thus, the role of endogenous glycine in the regulation of dopamine release remains unclear.


Author(s):  
James M. Kasper ◽  
Ashley E. Smith ◽  
Sierra N. Miller ◽  
Ara ◽  
William K. Russell ◽  
...  

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