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Cholecystokinin inhibits evoked inhibitory postsynaptic currents in the rat nucleus accumbens indirectly through γ‐aminobutyric acid and γ‐aminobutyric acid type B receptors
Author(s) -
Kombian Samuel B.,
Ananthalakshmi Kethireddy V.V.,
Parvathy Subramanian S.,
Matowe Wandikayi C.
Publication year - 2004
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/jnr.20349
Subject(s) - nucleus accumbens , inhibitory postsynaptic potential , chemistry , medicine , cholecystokinin , endocrinology , postsynaptic potential , neurotransmission , excitatory postsynaptic potential , receptor , dopamine , biology , biochemistry
We recently reported that cholecystokinin (CCK) excited nucleus accumbens (NAc) cells and depressed excitatory synaptic transmission indirectly through γ‐aminobutyric acid (GABA), acting on presynaptic GABA B receptors (Kombian et al. [2004] J. Physiol. 555:71–84). The present study tested the hypothesis that CCK modulates inhibitory synaptic transmission in the NAc. Using in vitro forebrain slices containing the NAc and whole‐cell patch recording, we examined the effects of CCK on evoked inhibitory postsynaptic currents (IPSCs) recorded at a holding potential of −80 mV throughout CCK‐8S caused a reversible inward current accompanied by a concentration‐dependent decrease in evoked IPSC amplitude. Maximum IPSC depression was ∼25% at 10 μM, with an estimated EC 50 of 0.1 μM. At 1 μM, CCK‐8S induced an inward current of 28.3 ± 4.8 pA (n = 6) accompanied by an IPSC depression of −18.8% ± 1.6% (n = 6). This CCK‐induced IPSC depression was blocked by pretreatment with proglumide (100 μM; −3.7% ± 6.9%; n = 4) and by LY225910 (100 nM), a selective CCK B receptor antagonist (4.4% ± 2.6%; n = 4). It was not blocked by SCH23390 (10 μM; −23.5% ± 1.3%; P < 0.05; n = 7) or sulpiride (10 μM; −21.8% ± 5.1%; P < 0.05; n = 4), dopamine receptor antagonists. By contrast, it was blocked by CGP55845 (1 μM; −0.4% ± 3.4%; n = 5) a potent GABA B receptor antagonist, and by forskolin (50 μM; 9.9% ± 5.2%; n = 4), an adenylyl cyclase activator, and H‐89 (1 μM; 6.9% ± 3.9%; n = 4), a protein kinase A (PKA) inhibitor. These results indicate that CCK acts on CCK B receptors to increase extracellular levels of GABA, which then acts on GABA B receptors to decrease IPSC amplitude. © 2004 Wiley‐Liss, Inc.