Electrophysiological Evidence for Expression of Glycine Receptors in Freshly Isolated Neurons from Nucleus Accumbens

Martin, Gilles E.; Siggins, George R.

doi:10.1124/jpet.102.033399

Cited by 51 publications

(51 citation statements)

References 63 publications

(71 reference statements)

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“…We used young male Sprague Dawley rats (80 -150 gm) to prepare NAcc slices as described previously (Martin and Siggins, 2002). Briefly, after decapitation, the brains were rapidly transferred into a cold (4°C), oxygenated, lowcalcium HEPES-buffered salt solution containing the following (in mM): 234 sucrose, 2.5 KCl, 2 NaH 2 PO 4 , 11 glucose, 4 MgSO 4 , 2 CaCl 2 , 1.5 HEPES.…”

Section: Methodsmentioning

confidence: 99%

Somatic Localization of a Specific Large-Conductance Calcium-Activated Potassium Channel Subtype Controls Compartmentalized Ethanol Sensitivity in the Nucleus Accumbens

Martin¹,

Puig²,

Pietrzykowski³

et al. 2004

J. Neurosci.

121

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Alcohol is an addictive drug that targets a variety of ion channels and receptors. To address whether the effects of alcohol are compartment specific (soma vs dendrite), we examined the effects of ethanol (EtOH) on large-conductance calcium-activated potassium channels (BK) in cell bodies and dendrites of freshly isolated neurons from the rat nucleus accumbens (NAcc), a region known to be critical for the development of addiction. Compartment-specific drug action was indeed observed. Clinically relevant concentrations of EtOH increased somatic but not dendritic BK channel open probability. Electrophysiological single-channel recordings and pharmacological analysis of the BK channel in excised patches from each region indicated a number of differences, suggestive of a compartment-specific expression of the ␤4 subunit of the BK channel, that might explain the differential alcohol sensitivity. These parameters included activation kinetics, calcium dependency, and toxin blockade. Reverse transcription-PCR showed that both BK channel ␤1 and ␤4 subunit mRNAs are found in the NAcc, although the signal for ␤1 is significantly weaker. Immunohistochemistry revealed that ␤1 subunits were found in both soma and dendrites, whereas ␤4 appeared restricted to the soma. These findings suggest that the ␤4 subunit may confer EtOH sensitivity to somatic BK channels, whereas the absence of ␤4 in the dendrite results in insensitivity to the drug. Consistent with this idea, acute EtOH potentiated ␣␤4 BK currents in transfected human embryonic kidney cells, whereas it failed to alter ␣␤1 BK channel-mediated currents. Finally, an EtOH concentration (50 mM) that increased BK channel open probability strongly decreased the duration of somatic-generated action potential in NAcc neurons.

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Section: Methodsmentioning

confidence: 99%

Somatic Localization of a Specific Large-Conductance Calcium-Activated Potassium Channel Subtype Controls Compartmentalized Ethanol Sensitivity in the Nucleus Accumbens

Martin¹,

Puig²,

Pietrzykowski³

et al. 2004

J. Neurosci.

121

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“…We used male Sprague-Dawley rats (100 -200 g) to prepare NAcc slices and isolated neurons as previously reported (Martin and Siggins, 2002;Martin et al, 2004). The rats were anesthetized with 4% halothane and decapitated, and the brains were rapidly transferred into a cold (4°C) oxygenated, low-calcium HEPES-buffered salt solution: 234 mM sucrose, 2.5 mM KCl, 2 mM NaH 2 PO 4 , 11 mM glucose, 4 mM MgSO 4 , 2 mM CaCl 2 , 1.5 mM HEPES.…”

Section: Methodsmentioning

confidence: 99%

Chronic Morphine Treatment AltersN-Methyl-d-aspartate Receptors in Freshly Isolated Neurons from Nucleus Accumbens

Martin

Guadaño-Ferraz²,

Morte³

et al. 2004

J Pharmacol Exp Ther

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Although there is now evidence of a role for N-methyl-D-aspartate (NMDA) receptors in nucleus accumbens (NAcc) neurons in the effects of chronic opiate treatment, the cellular and molecular mechanisms underlying this phenomenon are still unclear. Therefore, we studied the effects of chronic morphine on the pharmacological and biophysical properties of NMDA receptors in freshly isolated medium spiny neurons from NAcc. We found that chronic morphine treatment did not alter the affinity for NMDA receptor agonists such as glutamate, homoquinolinic acid, and NMDA, but decreased the affinity of glycine, the allosteric NMDA receptor coagonist, from 2.24 Ϯ 0.15 M to 5.1 Ϯ 1.45 M. Chronic morphine treatment also altered the affinity of two noncompetitive NMDA receptor antagonists, 7-chloro-kynurenic acid and ifenprodil. However, morphine had no effect on a third antagonist, D-(Ϫ)-2-amino-5-phosphonopentanoic acid. Single-exponential fits of desensitized NMDA current tails gave tau values ranging from 0.5 to 4 s in neurons from both control and morphine-treated rats. However, a shift to the left of the distribution of tau values after morphine treatment revealed that NMDA current desensitization rate was accelerated in a majority of NAcc neurons. Taken together with our recent molecular studies, our data are consistent with a shift away from NMDA receptor subunit (NR) NR2B and 2C function toward increased NR2A subunit expression or function after chronic morphine, a process that could alter excitability and integrative properties and may represent a neuroadaptation of NAcc medium spiny neurons underlying morphine dependence.During the past decade the nucleus accumbens, an interface between limbic regions and the extrapyramidal motor system, has emerged as a key structure mediating the acute and chronic behavioral effects of drugs of abuse (Koob et al., 1992). Although behavioral studies conclusively demonstrated a key role for NAcc in opiate self-administration, relatively little is known about the cellular and molecular mechanisms responsible for acute opiate effects, and even more remains to be understood about chronic effects. Recently, NMDA receptors have been recognized as a critical factor underlying tolerance to various drugs of abuse. Trujillo and Akil (1991) and Marek et al. (1991) were the first to report that intraventricular infusion of MK-801 (dizocilpine maleate), a selective noncompetitive NMDA receptor antagonist, could strongly attenuate the morphine withdrawal syndrome, a finding subsequently confirmed by others (Tiseo et al., 1994;Elliott et al., 1995).Numerous studies established that NMDA receptors, formed by the association of two or more subunits, have multiple binding sites for various agents such as endogenous agonists, competitive antagonists, and Mg 2ϩ , Zn 2ϩ , or polyamines. To date, five NMDA receptors subunits (NR1, NR2A-D) have been identified. It is believed that, in native NMDA receptors, these subunits are assembled in various combinations to create heteromultimeric receptors. In...

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“…Functional GlyRs have been found in the striatum (Sergeeva 1998) and the mature NAcc (Martin and Siggins 2002), although these areas contain few Gly-immunoreactive cell bodies and fibers (Rampon et al 1996). However, taurine (Tau), a putative agonist of GlyRs, is abundant in NAcc (Dahchour et al 1996;Madsen et al 1987).…”

Section: Introductionmentioning

confidence: 99%

“…Having a strychnine-sensitive, Gly-like action on many cells (Curtis et al 1968;Krnjević and Puil 1976;Legendre 2001;Mori et al 2002), Tau has been proposed as a candidate inhibitory transmitter (Curtis et al 1968;Davison and Kaczmarek 1971;Kaczmarek 1976;Padjen et al 1989). In a recent study on NAcc neurons isolated from adult rats, Martin and Siggins (2002) found that Gly and Tau elicited similar Cl Ϫ current in many cells; but these currents were relatively insensitive to strychnine and quite resistant to picrotoxin (PTX).…”

Section: Introductionmentioning

confidence: 99%

“…It is now clear that Gly-containing fibers and cell bodies and Gly receptors (GlyRs) are widely distributed in the CNS (Betz 1991;Malosio et al 1991;Rampon et al 1996). Gly and other GlyR agonists can elicit Cl Ϫ -mediated responses in neurons from many brain regions, including the cerebral cortex (Kilb et al 2002), striatum (Sergeeva 1998), nucleus accumbens (Martin and Siggins 2002), amygdala (McCool and Botting 2000), hippocampus (Chattipakorn and McMahon 2002;Krishtal et al 1988;Mori et al 2002;Ye et al 1999b), hypothalamus (Akaike and Kaneda 1989;Tokutomi et al 1989;Ye and McArdle 1996), and VTA (Ye et al 1998), indicating a wide distribution of functional GlyRs in the CNS.…”

Section: Introductionmentioning

confidence: 99%

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Taurine Activates Strychnine-Sensitive Glycine Receptors in Neurons Freshly Isolated From Nucleus Accumbens of Young Rats

Jiang¹,

Krnjević

Wang³

et al. 2004

Journal of Neurophysiology

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. Although functional glycine receptors (GlyRs) are present in the mature nucleus accumbens (NAcc), an important area of the mesolimbic dopamine system involved in drug addiction, their role has been unclear because the NAcc contains little glycine. However, taurine, an agonist of GlyRs, is abundant throughout the brain, especially during early development. In the present study on freshly dissociated NAcc neurons from young Sprague-Dawley rats (12-to 21-day old), we found that both glycine and taurine can strongly depolarize NAcc neurons and modulate their excitability. In voltage-clamped NAcc neurons, glycine and taurine elicited chloride currents (I Gly and I Tau ) with an EC 50 of 0.12 and 1.25 mM, respectively. The reversal potential of I Gly or I Tau was 0 mV in conventional whole cell mode and -30 mV in gramicidin-perforated mode. At concentrations Ͻ1 mM, both glycine and taurine were very effectively antagonized by strychnine and by picrotoxin (with an IC 50 of 60 nM and 36.5 M for I Gly , and 40 nM and 42.2 M for I Tau ) but were insensitive to 10 M bicuculline. The currents elicited by taurine (Յ1 mM) showed complete cross-desensitization with I Gly , but none with ␥-aminobutyric acid (GABA)-induced currents (I GABA ). However, I Tau elicited by very concentrated taurine (10 mM) showed partial cross-desensitization with I GABA , and it was substantially antagonized by 10 M bicuculline. These results indicate that taurine binds mainly to GlyRs in NAcc, but it could be a partial agonist of GABA A receptors. By activating GlyRs, taurine may play an important physiological role in the control of NAcc function, especially during development.

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Electrophysiological Evidence for Expression of Glycine Receptors in Freshly Isolated Neurons from Nucleus Accumbens

Cited by 51 publications

References 63 publications

Somatic Localization of a Specific Large-Conductance Calcium-Activated Potassium Channel Subtype Controls Compartmentalized Ethanol Sensitivity in the Nucleus Accumbens

Somatic Localization of a Specific Large-Conductance Calcium-Activated Potassium Channel Subtype Controls Compartmentalized Ethanol Sensitivity in the Nucleus Accumbens

Chronic Morphine Treatment AltersN-Methyl-d-aspartate Receptors in Freshly Isolated Neurons from Nucleus Accumbens

Taurine Activates Strychnine-Sensitive Glycine Receptors in Neurons Freshly Isolated From Nucleus Accumbens of Young Rats

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