Nitrendipine, given during drinking, decreases the electrophysiological changes in the isolated hippocampal slice, seen during ethanol withdrawal

Whittington, Miles A.; Little, H.J.

doi:10.1111/j.1476-5381.1991.tb09846.x

Cited by 41 publications

(16 citation statements)

References 23 publications

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“…For instance, L-VGCC density is increased during chronic exposure, and hyperexcitability after ethanol withdrawal in vivo is inhibited by L-VGCC blockers (Dolin et al, 1987;Wu et al, 1987;Whittington and Little, 1991;Whittington et al, 1995, Gerstin et al, 1998. Whittington and Little (1989) also reported that dihydropyridines block hyperexcitability in hippocampal slices prepared from chronic ethanol-treated animals, whereas control slices were insensitive to these antagonists, a finding later reproduced in cultured Purkinjie neurons (Gruol and Parsons, 1994).…”

Section: Vgcc-dependent Synaptic Effects Of Ethanolmentioning

confidence: 95%

Suppression of L-Type Voltage-Gated Calcium Channel-Dependent Synaptic Plasticity by Ethanol: Analysis of Miniature Synaptic Currents and Dendritic Calcium Transients

Hendricson

Thomas

Lippmann

et al. 2003

J Pharmacol Exp Ther

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Intoxicating concentrations of ethanol inhibit N-methyl-D-as-partate (NMDA) receptor-dependent long-term potentiation, an interaction thought to underlie a major component of the central nervous system actions of ethanol. Another form of synaptic potentiation involving activation of L-type dihydropyridinesensitive voltage-gated calcium channels (VGCCs) has been described, but very little information concerning ethanol effects on VGCC-dependent synaptic potentiation is available. Here, we assessed ethanol effects on VGCC-dependent synaptic potentiation using whole cell patch-clamp recordings of ␣-amino-3-hydroxy-5-methyl-4-soxazolepropionic acid (AMPA) receptor-mediated miniature excitatory postsynaptic currents (mEPSCs) in area CA1 of the rat hippocampus. No potentiation was observed in artificial cerebrospinal fluid containing 2 to 3 mM Ca 2ϩ , but marked potentiation of mEPSCs was consistently observed in 4 mM Ca 2ϩ and with patch pipettes containing an ATP-regenerating system. This potentiation was insensitive to the NMDA receptor antagonist DL-2-amino-5-phosphonovaleric acid, whereas it was completely blocked the L-type VGCC antagonist nifedipine. Potentiation was also blocked dose dependently by bath application of ethanol (25-75 mM), which had no effect on baseline mEPSC amplitude or frequency. The synaptic potentiation involved enhancement of both presynaptic and postsynaptic components because significant increases in both the frequency and amplitude of AMPA mEPSCs were observed. Ethanol inhibition of VGCCdependent synaptic potentiation seemed to occur at the induction step because both the increases in mEPSC frequency and amplitude were affected. To address that question more directly, we used fluorescent imaging of synaptically evoked dendritic calcium events, which displayed a similarly marked ethanol sensitivity. Thus, ethanol modulates fast excitatory synaptic transmission by inhibiting the induction of an NMDA receptor-independent form of synaptic potentiation observed at excitatory synapses on central neurons.Efforts directed toward unraveling the synaptic basis for alcohol-related brain disorders have centered upon direct ethanol effects on the major excitatory and inhibitory ligandgated ion channels (LGICs) operated by GABA A and NMDA receptors (NMDARs). Indeed, the direct actions of ethanol on NMDARs impact the functional properties of neurons and profoundly alter the short-term processing and long-term storage of information in neural networks (Durand and

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Section: Vgcc-dependent Synaptic Effects Of Ethanolmentioning

confidence: 95%

Suppression of L-Type Voltage-Gated Calcium Channel-Dependent Synaptic Plasticity by Ethanol: Analysis of Miniature Synaptic Currents and Dendritic Calcium Transients

Hendricson

Thomas

Lippmann

et al. 2003

J Pharmacol Exp Ther

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“…We have demonstrated by electrophysiological studies (Whittington & Little, 1989a,b;Whittington & Little, 1991b) that nitrendipine prevented the evidence of neuronal hyperexcitability seen in isolated hippocampal slices following chronic ethanol administration in vivo. This action of nitrendipine was seen whether the compound was added to the perfusion medium during the electrophysiological recording or given to the animals during the chronic ethanol treatment, as in the present study.…”

Section: Central Dihydropyridine Bindingmentioning

confidence: 96%

Chronic dihydropyridine treatment can reverse the behavioural consequences of and prevent adaptations to, chronic ethanol treatment

Whittington¹,

Dolin²,

Patch³

et al. 1991

British J Pharmacology

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1 Chronic treatment with the dihydropyridine calcium channel antagonist, nitrendipine, given concurrently with ethanol, prevented the ethanol withdrawal syndrome in mice, even though the chronic nitrendipine treatment was stopped 24 h or 48 h before the withdrawal testing. 2 This effect was seen in two strains of mice with different methods of ethanol administration. Nitrendipine was effective when given for two weeks but not after only two days' treatment. 3 Two other dihydropyridine calcium antagonists, nimodipine and PN 200-110, given chronically with ethanol, also prevented the withdrawal syndrome. The tests were again made 24 h after the last administration of dihydropyridine. 4 The chronic nitrendipine treatment also prevented the rise in the number of central dihydropyridine binding sites that occurs on chronic ethanol administration. 5 Chronic administration of nitrendipine alone did not cause any withdrawal behaviour. 6 Chronic nitrendipine treatment did not affect the seizure threshold to bicuculline in mice that were not given ethanol. 7 Whole brain concentration measurements showed that the effects were not due to residual nitrendipine in the CNS at the time of withdrawal testing or to differences in central ethanol concentrations during the treatment.8 It is suggested that the results provide evidence for a functional role for dihydropyridine-sensitive calcium channels in ethanol dependence.

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“…These experiments indicate that a selective enhancement of spikedependent release after WD from chronic exposure occurred and implicate ethanol-sensitive components of spike-dependent release in the pathophysiology of WD. It is interesting to note that voltage-gated calcium channel antagonists reduce behavioral WD manifestations after chronic exposure (Little et al, 1986;Wu et al, 1987;Whittington and Little, 1991), and ethanol is also well known to directly block VGCCs (Harris and Hood, 1980;Hendricson et al, 2003); in particular, N and P/Q-type channels that are known to subserve jpet.aspetjournals.org transmitter release in multiple brain preparations (Woodward et al, 1990;Wang et al, 1991;Maldve et al, 2004).…”

Section: Discussionmentioning

confidence: 99%

Aberrant Synaptic Activation ofN-Methyl-d-aspartate Receptors Underlies Ethanol Withdrawal Hyperexcitability

Hendricson

Maldve²,

Salinas³

et al. 2007

J Pharmacol Exp Ther

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Chronic ethanol exposure may induce neuroadaptive responses in N-methyl-D-aspartate (NMDA) receptors, which are thought to underlie a variety of alcohol-related brain disorders. Here, we demonstrate that hyperexcitability triggered by withdrawal from chronic ethanol exposure is associated with increases in both synaptic NMDA receptor expression and activation. Withdrawal from chronic ethanol exposure (75 mM ethanol, 5-9 days) elicited robust and prolonged epileptiform activity in CA1 pyramidal neurons from hippocampal explants, which was absolutely dependent upon NMDA receptor activation but independent of chronic inhibition of protein kinase A (PKA). Analysis of Sr 2ϩ -supported asynchronous NMDA receptor-mediated miniature excitatory postsynaptic currents (mEPSCs) was employed to assess changes in NMDA neurotransmission. After chronic exposure, ethanol withdrawal was associated with an increase in mEPSC amplitude 3.38-fold over that after withdrawal from acute ethanol exposure. Analysis of paired evoked ␣-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid EPSCs and spontaneous mEPSCs indicated that withdrawal after chronic exposure was also associated with a selective increase in action potential evoked but not spontaneous transmitter release probability. Immunoblot analysis revealed significant increases in total NR1, NR2A, and NR2B subunit expression after chronic exposure and unaffected by PKA-inhibition manner. Confocal imaging studies indicate that increased NR1 subunit expression was associated with increased density of NR1 expression on dendrites in parallel with a selective increase in the size of NR1 puncta on dendritic spines. Therefore, neuroadaptation to chronic ethanol exposure in NMDA synaptic transmission is responsible for aberrant network excitability after withdrawal and results from changes in both postsynaptic function as well as presynaptic release.

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Nitrendipine, given during drinking, decreases the electrophysiological changes in the isolated hippocampal slice, seen during ethanol withdrawal

Cited by 41 publications

References 23 publications

Suppression of L-Type Voltage-Gated Calcium Channel-Dependent Synaptic Plasticity by Ethanol: Analysis of Miniature Synaptic Currents and Dendritic Calcium Transients

Suppression of L-Type Voltage-Gated Calcium Channel-Dependent Synaptic Plasticity by Ethanol: Analysis of Miniature Synaptic Currents and Dendritic Calcium Transients

Chronic dihydropyridine treatment can reverse the behavioural consequences of and prevent adaptations to, chronic ethanol treatment

Aberrant Synaptic Activation ofN-Methyl-d-aspartate Receptors Underlies Ethanol Withdrawal Hyperexcitability

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