Baclofen and adenosine inhibit synaptic potentials mediated by gamma-aminobutyric acid and glutamate release in rat nucleus accumbens.
Intracellular recordings were made from rat nucleus accumbens neurons in a tissue slice in vitro; postsynaptic potentials (p.s.p.) were evoked by focal electrical stimulation of the slice surface. P.s.p. were partially blocked by bicuculline (30 microM), partially blocked by a combination of 6-cyano-2,3-dihydroxy-7-nitroquinoxaline (CNQX, 10 microM) and DL-2-amino-5-phosphonovaleric acid (APV, 30 microM) and completely blocked when all three antagonists were applied together. Both the gamma-aminobutyric acid (GABA)-mediated p.s.p. (in CNQX and APV) and the glutamate-mediated p.s.p. (in bicuculline) were inhibited by baclofen (10-300 microM), adenosine (10-300 microM) and N6-(2-phenylisopropyl)adenosine (0.1-3 microM). Theophylline competitively antagonized the action of adenosine with an apparent dissociation equilibrium constant of about 15 microM. Baclofen, adenosine and N6-(2-phenylisopropyl)adenosine caused small (less than 10 mV) hyperpolarizations; voltage clamp experiments indicated that this resulted from an outward potassium current. It is concluded that activation of GABAB receptors and adenosine A1 receptors inhibits the release of glutamate and GABA at synapses in the nucleus accumbens.
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Vollum Institute, Oregon Health Sciences University, Portland.
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D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D000200:Action Potentials / Q000187:drug effects; D000241:Adenosine / Q000494:pharmacology*; D000818:Animals; D001418:Baclofen / Q000494:pharmacology*; D001640:Bicuculline / Q000494:pharmacology; D005971:Glutamates / Q000378:metabolism* / Q000494:pharmacology; D018698:Glutamic Acid; D066298:In Vitro Techniques; D008564:Membrane Potentials / Q000187:drug effects; D009714:Nucleus Accumbens / Q000187:drug effects / Q000502:physiology*; D010660:Phenylisopropyladenosine / Q000494:pharmacology; D011810:Quinoxalines / Q000494:pharmacology; D051381:Rats; D011963:Receptors, GABA-A / Q000187:drug effects; D011983:Receptors, Purinergic / Q000187:drug effects; D013569:Synapses / Q000502:physiology*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism* / Q000494:pharmacology
D005971:Glutamates; D011810:Quinoxalines; D011963:Receptors, GABA-A; D011983:Receptors, Purinergic; D010660:Phenylisopropyladenosine; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D015763:2-Amino-5-phosphonovalerate; D001418:Baclofen; D000241:Adenosine; D001640:Bicuculline