Acute Immobilization Stress Modulate GABA Release from Rat Olfactory Bulb: Involvement of Endocannabinoids—Cannabinoids and Acute Stress Modulate GABA Release

Alejandra Delgado,Erica H Jaffé

doi:10.1155/2011/529851

Alejandra Delgado, Erica H Jaffé

Open Access

https://doi.org/10.1155/2011/529851

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Abstract

We studied the effects of cannabinoids and acute immobilization stress on the regulation of GABA release in the olfactory bulb. Glutamate-stimulated 3H-GABA release was measured in superfused slices. We report that cannabinoids as WIN55, 212-2, methanandamide, and 2-arachidonoylglycerol were able to inhibit glutamate- and KCl-stimulated 3H-GABA release. This effect was blocked by the CB1 antagonist AM281. On the other hand, acute stress was able per se to increase endocannabinoid activity. This effect was evident since the inhibition of stimulated GABA release by acute stress was reversed with AM281 and tetrahydrolipstatin. Inhibition of the endocannabinoid transport or its catabolism showed reduction of GABA release, antagonized by AM281 in control and stressed animals. These results point to endocannabinoids as inhibitory modulators of GABA release in the olfactory bulb acting through an autocrine mechanism. Apparently, stress increases the endocannabinoid system, modulating GABAergic synaptic function in a primary sensory organ.

Highlights

Cannabinoids comprise a family of lipids/eicosanoids, derived from marijuana/Hashish (Cannabis sativa)
Micro dissected external plexiform layer (EPL) (Figure 1(b)) was preincubated in 1.5 mL Krebs bicarbonate solution at 25◦C for 10 min. (in mM: KCl 2,5; KH2P04 1.25; MgCl 1, NaCl 125; CaCl2 2; glucose 10, NaHC03 26; aminooxyacetic acid (AOAA) 10 μM; and equilibrated with 02/C02 to pH 7.4). 3H-GABA was added to a final concentration of 0.1 μM and incubation continued for 15 min under continuous oxygenation with 95% 02/5% CO2
0.94∗ (0.61–1.06) n:6 0.53ns (0.41–0.6) n : 26 0.42ns (0.36–0.54) n : 30 cannabinoid receptors have been described in the olfactory bulb and olfactory epithelium [9,10,11, 35, 51]

Summary

Introduction

Cannabinoids comprise a family of lipids/eicosanoids, derived from marijuana/Hashish (Cannabis sativa) They may be endogenous to animals (endocannabinoids) or synthetically produced (cannabimimetic) [1, 2]. Cannabinoids play a critical neuromodulatory role in the central and peripheral nervous system, as well as in the immune system, being an emerging therapeutic target for several disorders as addiction, obesity, nauseas and vomiting, pain, mental disorders, spasticity, glaucoma, and others [1, 3,4,5] They may be associated with an old and widely used drug as acetaminophen/paracetamol, which is metabolized to a bioactive cannabimimetic drug AM404, an inhibitor of endocanabinoid uptake [6, 7]. The transporter of eCB is important in regulating the activity of the cannabinoid system in the CNS [5, 19, 20]

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