γ-Hydroxybutyrate (GHB) induces GABAB receptor independent intracellular Ca2+ transients in astrocytes, but has no effect on GHB or GABAB receptors of medium spiny neurons in the nucleus accumbens

• Published in: Neuroscience 2009-08, Vol.162 (2), p.268-281
• Main Authors: Molnár, T, Antal, K, Nyitrai, G, Emri, Z
• Format: Article
• Language: English
• Subjects: Biological and medical sciences; Fundamental and applied biological sciences. Psychology; Neurology; Vertebrates: nervous system and sense organs
• ISSN: 0306-4522; 1873-7544
• DOI: 10.1016/j.neuroscience.2009.05.017

Abstract We report on cellular actions of the illicit recreational drug γ-hydroxybutyrate (GHB) in the brain reward area nucleus accumbens. First, we compared the effects of GHB and the GABAB receptor agonist baclofen. Neither of them affected the membrane currents of medium spiny neurons in rat nucleus accumbens slices. GABAergic and glutamatergic synaptic potentials of medium spiny neurons, however, were reduced by baclofen but not GHB. These results indicate the lack of GHB as well as postsynaptic GABAB receptors, and the presence of GHB insensitive presynaptic GABAB receptors in medium spiny neurons. In astrocytes GHB induced intracellular Ca2+ transients, preserved in slices from GABAB receptor type 1 subunit knockout mice. The effects of tetrodotoxin, zero added Ca2+ with/without intracellular Ca2+ store depletor cyclopiazonic acid or vacuolar H-ATPase inhibitor bafilomycin A1 indicate that GHB-evoked Ca2+ transients depend on external Ca2+ and intracellular Ca2+ stores, but not on vesicular transmitter release. GHB-induced astrocytic Ca2+ transients were not affected by the GHB receptor-specific antagonist NCS-382, suggesting the presence of a novel NCS-382-insensitive target for GHB in astrocytes. The activation of astrocytes by GHB implies their involvement in physiological actions of GHB. Our findings disclose a novel profile of GHB action in the nucleus accumbens. Here, unlike in other brain areas, GHB does not act on GABAB receptors, but activates an NCS-382 insensitive GHB-specific target in a subpopulation of astrocytes. The lack of either post- or presynaptic effects on medium spiny neurons in the nucleus accumbens distinguishes GHB from many drugs and natural rewards with addictive properties and might explain why GHB has only a weak reinforcing capacity.