Ethanol Modulation of gamma-Aminobutyric Acid (GABA)-Mediated Inhibition of Cerebellar Purkinje Neurons: Relationship to GABAb Receptor Input

AbstractPrevious studies suggest that signaling by the gamma-aminobutyric acid (GABA) type B receptor (GABABR) is involved in the regulation of binge eating, a disorder which might contribute to the development of obesity. Here, we show that intermittent access to a high fat diet (HFD) induced binge-like eating behavior with activation of dopamine receptor d1 (drd1)-expressing neurons in the caudate putamen (CPu) and nucleus accumbens (NAc) in wild-type (WT) mice. The activation of drd1-expressing neurons during binge-like eating was substantially increased in the CPu, but not in the NAc, in corticostriatal neuron-specific GABABR-deficient knockout (KO) mice compared to WT mice. Treatment with the GABABR agonist, baclofen, suppressed binge-like eating behavior in WT mice, but not in KO mice, as reported previously. Baclofen also suppressed the activation of drd1-expressing neurons in the CPu, but not in the NAc, during binge-like eating in WT mice. Thus, our data suggest that GABABR signaling in CPu neurons expressing drd1 suppresses binge-like consumption during a HFD in mice.

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Tetanus-induced sustained potentiation of monosynaptic inhibitory transmission in the rat medulla: evidence for a presynaptic locus

Journal of Neurophysiology ◽

10.1152/jn.1996.76.1.30 ◽

1996 ◽

Vol 76 (1) ◽

pp. 30-38 ◽

Cited By ~ 29

Author(s):

S. R. Glaum ◽

P. A. Brooks

Keyword(s):

Channel Blocker ◽

Gabab Receptor ◽

Cell Voltage ◽

Synaptic Activity ◽

Aminobutyric Acid ◽

Gamma Aminobutyric Acid ◽

Dorsomedial Nucleus ◽

Inhibitory Transmission ◽

Voltage Dependent ◽

Gabab Receptor Antagonist

1. Whole cell voltage-clamp recordings were made from dorsomedial nucleus tractus solitarii (dmNTS) neurons in coronal rat medullary slices. Synaptic activity was evoked by electrical stimulation in the region of the tractus solitarius (TS). Excitatory postsynaptic current/inhibitory postsynaptic current (EPSC/IPSC) complexes were recorded with K-gluconate-containing electrodes. Monosynaptic, gamma-aminobutyric acid-A (GABAA) receptor-mediated evoked IPSCs (evIPSCs) were recorded in the presence of D(-)2-amino-5-phosphonopentanoic acid (AP5, 50 microM) and 6,7-dinitroquinoxaline-2,3-dione (DNQX, 10 microM) with CsCl-containing electrodes. Control synaptic stimulation was applied at 0.1 Hz. 2. Tetanic stimulation (50 Hz, 2 s) produced an increase in the 10-90% rise time of the evIPSC component of mixed EPSC/IPSC complexes (assessed at Vhold = 0 mV) in three of eight recordings that remained significantly potentiated above control for > 15 min. This potentiation was further characterized with the use of Cs-containing electrodes. Tetanus similarly potentiated the amplitude of monosynaptic evIPSCs by 168.0 +/- 10.4% (mean +/- SE) control at 15 min posttetanus in 49 of 114 recordings. This tetanus-induced sustained potentiation of monosynaptic evIPSCs (TIP) was reproducible after recovery to control levels. 3. High Mg2+/low Ca2+ solutions reversibly blocked induction of TIP. TIP was reproducible in slices treated (> 7 min) with the N-type voltage-dependent Ca2+ channel (VDCC) antagonist omega-conotoxin-GVIA (1 microM) or L-type channel blocker nimodipine (10 microM), but not in those slices treated with either omega-agatoxin-IVA (200 nM, 20 min) or omega-conotoxin-MVIIC (2 microM). 4. The GABAB receptor antagonist CGP35348 (100 microM) reversibly blocked induction of TIP, reduced resting, and blocked tetanus-induced increases in spontaneous IPSC frequency. Spontaneous IPSC amplitude was unaffected by CGP35348. 5. These results suggest a presynaptic locus for TIP in dmNTS, which depends in part on Ca2+ influx through P/Q-type VDCCs.

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