8‐Bromo‐cAMP Mimics β‐Adrenergic Sensitization of GABA Responses to Ethanol in Cerebellar Purkinje Neurons <i>in vivo</i>

Freund, Ronald K.; Palmer, Michael R.

doi:10.1111/j.1530-0277.1996.tb01661.x

Cited by 17 publications

(9 citation statements)

References 31 publications

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“…Therefore, antagonism of constitutively activated GABAB receptors, as might occur in our study, should then lead to enhanced cyclic AMP levels and PKA activity. This idea is consistent with cerebellar data suggesting that adenylyl cyclase and PKA activation is necessary for ethanol potentiation of GABA responses (57,58). GABAB receptor activation has also been shown to reduce PKC activation (59), postulated by Weiner et al (11) to be required for ethanol potentiation of IPSPs in hippocampal slices.…”

Section: Discussionsupporting

confidence: 88%

Low ethanol concentrations enhance GABAergic inhibitory postsynaptic potentials in hippocampal pyramidal neurons only after block of GABAB receptors.

Wan

Berton

Madamba

et al. 1996

Proc. Natl. Acad. Sci. U.S.A.

130

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Despite considerable evidence that ethanol can enhance chloride flux through the y-aminobutyric acid type A (GABAA) receptor-channel complex in several central neuron types, the effect ofethanol on hippocampal GABAergic systems is still controversial. Therefore, we have reevaluated this interaction in hippocampal pyramidal neurons subjected to local monosynaptic activation combined with pharmacological isolation of the various components of excitatory and inhibitory synaptic potentials, using intracellular currentand voltage-clamp recording methods in the hippocampal slice. In accord with our previous findings, we found that ethanol had little effect on compound inhibitory postsynaptic potentials/currents (IPSP/Cs) containing both GABAA and GABAB components. However, after selective pharmacological blockade of the GABAB component of the IPSP (GABAB-IPSP/C) by low It is common knowledge that alcohol intoxication and the resulting loss of motor and cognitive control in humans have led to untold trauma and suffering. Despite the likelihood that such problems arise from the action of ethanol on the central nervous system (CNS) and several decades of alcohol research suggesting a general depressant effect of intoxicating doses of ethanol on CNS neurons, until recently little has been known about the mechanisms behind this depression. Studies over the past decade have shown that the most sensitive site for ethanol action is the synapse (1-5), and more recently it has been suggested that ethanol-evoked neuronal depression might arise from either a blunting of excitatory glutamatergic synaptic transmission (see, e.g., refs. 6-8) and/or an enhancement of inhibitory y-aminobutyric acid (GABA)ergic transmission (see refs. 4 and 9).With regard to inhibitory neurotransmission, ethanol has often been reported to enhance GABAA receptor activation, and the resulting Cl-currents or fluxes, in neurons or isolated preparations of several brain regions (4,9 (see refs. 24-26). In addition, the development of local or focal stimulation techniques (27,28), combined with these selective antagonists, now allows study of pharmacologically isolated synaptic components. Therefore, we have repeated earlier studies of ethanol effects on GABAergic monosynaptic IPSPs with two different slice preparation methods, including the one used in previous studies from our laboratory (13), but now with pharmacologically isolated IPSP components. We now report that, under these conditions, low ethanol concentrations reproducibly enhance GABAAergic IPSPs of hippocampal pyramidal neurons (HPNs), but only when GABAB receptors are blocked.MATERIALS AND METHODS Preparation. The two hippocampal slice preparations used were as described (13,29,30). In brief, male Sprague-Dawley Abbreviations: IPSP/C, inhibitory postsynaptic potential/current; IPSC, inhibitory postsynaptic current; HPN, hippocampal pyramidal neuron; GABA, y-aminobutyric acid; CNQX, 6-cyano-7-nitroquinoxaline-2,3-dione; d-APV, DL-2-amino-5-phosphonovaleric acid; ACSF, artificial cer...

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Section: Discussionsupporting

confidence: 88%

Low ethanol concentrations enhance GABAergic inhibitory postsynaptic potentials in hippocampal pyramidal neurons only after block of GABAB receptors.

Wan

Berton

Madamba

et al. 1996

Proc. Natl. Acad. Sci. U.S.A.

130

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“…The acute effects of alcohol on GABA-mediated inhibition of neuronal activity are dependent on other neurotransmitter and second messenger systems. For instance, alcohol potentiation of GABA inhibition of cerebellar Purkinje cell activity only is observed during simultaneous activation of ß-adrenergic receptor and protein kinase A (Lin et al, 1993;Freund and Palmer, 1996). The acute and chronic effects of alcohol on GABA-mediated function are different.…”

Section: Alcoholmentioning

confidence: 97%

Neuropsychology and neuropharmacology of P3a and P3b

Polich

Criado

2006

International Journal of Psychophysiology

637

491

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“…Previous reports indicate that activation of noradrenergic neurons modulates the electrophysiological depressant e¤ect of c-aminobutyric acid (GABA) (Moises et al 1979; Moises and Woodward 1980;Lee et al 1995). Local application of NE or isoproterenol (ISO) facilitates GABA-induced depression in cerebellar Purkinje neurons (ParÞtt et al 1990;Lin et al 1993b;Sessler et al 1995;Freund and Palmer 1996). Electrical stimulation of noradrenergic input in the locus coeruleus also potentiates cerebellar GABA responses, an e¤ect which can be antagonized by b-adrenergic antagonists.…”

Section: Introductionmentioning

confidence: 96%

Methamphetamine modulates GABA-induced electrophysiological depression by alternating noradrenergic actions in cerebellar Purkinje neurons

Jeng

Wang

1998

Psychopharmacology

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Previous studies have indicated that gamma-aminobutyric acid (GABA)-induced electrophysiological responses can be enhanced by noradrenaline (NE) acting via beta-adrenergic receptors. Methamphetamine (MA) has been reported to be a noradrenergic releasing agent. In the present study, we examined the interaction of MA and GABA in cerebellar Purkinje neurons of urethane-anesthetized rats. We found that local application of MA did not potentiate GABA-induced electrophysiological depressions in Purkinje neurons. Since MA may act indirectly or directly on alpha or beta noradrenergic receptors, we further examined the interactions of MA with selective noradrenergic antagonists. We found that after blocking alpha-adrenergic receptors with prazocin, MA significantly facilitated GABA responses. On the other hand, co-administration of timolol with MA did not attenuate GABA-induced neuronal depressions. To examine further the interactions between alpha and beta receptors in modulating GABA response, we found that stimulation of alpha-adrenergic receptors in the absence of beta receptor activation, such as by application of the alpha-agonist phenylephrine alone, did not decrease GABA-induced inhibition. However, stimulation of alpha-adrenergic receptors in the presence of beta-receptor activation, such as by co-application of phenylephrine and the beta-agonist isoproterenol (ISO), attenuated ISO-facilitated GABA inhibition. Taken together, these data suggest that MA may activate two noradrenergic modulatory mechanisms: beta-adrenergic receptor-induced GABA potentiation and alpha-adrenergic inhibition, which attenuates beta-mediated modulation. In conclusion, our data suggest that MA may regulate GABA-induced electrophysiological response by altering both the alpha- and beta-noradrenergic inputs in cerebellar Purkinje neurons.

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8‐Bromo‐cAMP Mimics β‐Adrenergic Sensitization of GABA Responses to Ethanol in Cerebellar Purkinje Neurons in vivo

Cited by 17 publications

References 31 publications

Low ethanol concentrations enhance GABAergic inhibitory postsynaptic potentials in hippocampal pyramidal neurons only after block of GABAB receptors.

Low ethanol concentrations enhance GABAergic inhibitory postsynaptic potentials in hippocampal pyramidal neurons only after block of GABAB receptors.

Neuropsychology and neuropharmacology of P3a and P3b

Methamphetamine modulates GABA-induced electrophysiological depression by alternating noradrenergic actions in cerebellar Purkinje neurons

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