Acute Ethanol Administration and Acute Allopregnanolone Administration Impair Spatial Memory in the Morris Water Task

Matthews, Douglas B.; Morrow, A. Leslie; Tokunaga, Sayaka; McDaniel, Janelle R.

doi:10.1111/j.1530-0277.2002.tb02479.x

Cited by 107 publications

(40 citation statements)

References 51 publications

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“…The work of multiple laboratories has produced a large body of evidence that suggests that ethanol-induced elevations of GABAergic neurosteroids contribute to several behavioral effects of ethanol, including ethanol’s memory-impairing effect (Kumar et al, 2009; Matthews et al, 2002; Morrow et al, 2001). Sanna et al (2004) have shown that in the hippocampal slice ethanol-induced de novo synthesis of the neurosteroid 3α,5α-THP mediates some of the ethanol enhancement of miniature and evoked IPSC amplitude that has been reported in CA1 neurons.…”

Section: Resultsmentioning

confidence: 99%

The effects of acute and chronic ethanol exposure on presynaptic and postsynaptic gamma-aminobutyric acid (GABA) neurotransmission in cultured cortical and hippocampal neurons

Fleming¹,

Manis²,

Morrow³

2009

Alcohol

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Decades after ethanol was first described as a GABA mimetic, the precise mechanisms that produce the acute effects of ethanol and the physiological adaptations that underlie ethanol tolerance and dependence remain unclear. While a substantial body of evidence suggests that ethanol acts on GABAergic neurotransmission to enhance inhibition in the CNS, the precise mechanisms underlying the physiological effects of both acute and chronic ethanol exposure are still under investigation. We have used in vitro ethanol exposure followed by recording of miniature inhibitory postsynaptic currents (mIPSCs) to determine whether acute or chronic ethanol exposure directly alters synaptic GABA A receptor function or GABA release in cultured cortical and hippocampal neurons. Acute ethanol exposure slightly increased the duration of mIPSCs in hippocampal neurons but did not alter mIPSC kinetics in cortical neurons. Acute ethanol exposure did not change mIPSC frequency in either hippocampal or cortical neurons. One day of chronic ethanol exposure produced a transient decrease in mIPSC duration in cortical neurons but did not alter mIPSC kinetics in hippocampal neurons. Chronic ethanol exposure did not change mIPSC frequency in either hippocampal or cortical neurons. Chronic ethanol exposure also did not produce substantial cross-tolerance to a benzodiazepine in either hippocampal or cortical neurons. The results suggest that ethanol exposure in vitro has limited effects on synaptic GABA A R function and action-potential independent GABA release in cultured neurons and suggests that ethanol exposure in cultured cortical and hippocampal neurons may not reproduce all of the effects that occur in vivo and in acute brain slices.

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Section: Resultsmentioning

confidence: 99%

The effects of acute and chronic ethanol exposure on presynaptic and postsynaptic gamma-aminobutyric acid (GABA) neurotransmission in cultured cortical and hippocampal neurons

Fleming¹,

Manis²,

Morrow³

2009

Alcohol

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“…A large body of evidence from multiple laboratories suggests that ethanol-induced elevations of GABAergic neuroactive steroids contribute to several behavioral effects of ethanol in rodents. Neuroactive steroids have been shown to modulate ethanol’s anticonvulsant effects (VanDoren et al 2000), sedation (Khisti et al 2003), impairment of spatial memory (Matthews et al 2002; Morrow et al 2001), anxiolytic-like (Hirani et al 2005), antidepressant-like (Hirani et al 2002), and pro-aggressive (Fish et al 2001) actions. Most of these behavioral responses are prevented by pretreatment with finasteride and/or by prior adrenalectomy (Hirani et al 2002; 2005; VanDoren et al 2000).…”

Section: Acute Effects Of Ethanol On Gabaa Receptorsmentioning

confidence: 99%

The role of GABAA receptors in the acute and chronic effects of ethanol: a decade of progress

et al. 2009

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The past decade has brought many advances in our understanding of GABA A receptor-mediated ethanol action in the central nervous system. We now know that specific GABA A receptor subtypes are sensitive to ethanol at doses attained during social drinking while other subtypes respond to ethanol at doses attained by severe intoxication. Furthermore, ethanol increases GABAergic neurotransmission through indirect effects, including the elevation of endogenous GABAergic neuroactive steroids, presynaptic release of GABA, and dephosphorylation of GABA A receptors promoting increases in GABA sensitivity. Ethanol's effects on intracellular signaling also influence GABAergic transmission in multiple ways that vary across brain regions and cell types. The effects of chronic ethanol administration are influenced by adaptations in GABA A receptor function, expression, trafficking, and subcellular localization that contribute to ethanol tolerance, dependence, and withdrawal hyperexcitability. Adolescents exhibit altered sensitivity to ethanol actions, the tendency for higher drinking and longer lasting GABAergic adaptations to chronic ethanol administration. The elucidation of the mechanisms that underlie adaptations to ethanol exposure are leading to a better understanding of the regulation of inhibitory transmission and new targets for therapies to support recovery from ethanol withdrawal and alcoholism.

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“…Benzodiazepine tranquilizers are amnestic (Veselis et al, 2009), as are certain anesthetics such as propofol (Veselis et al, 2009) and isoflurane (Saab et al, 2010). Both alcohol and the neurosteroid THP impair spatial learning on the Morris Water Maze (Matthews et al, 2002). In adult CA1 hippocampus, α5β3γ2 GABARs have high expression extrasynaptically where they localize to the dendritic shaft and to the base of the dendritic spine (Brunig et al, 2002).…”

Section: Positive Modulators Of Gabaa Receptors and Synaptic Plasticitymentioning

confidence: 99%

α4βδ GABAA receptors and tonic inhibitory current during adolescence: effects on mood and synaptic plasticity

Smith

2013

Front. Neural Circuits

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The onset of puberty is associated with alterations in mood as well as changes in cognitive function, which can be more pronounced in females. Puberty onset in female mice is associated with increased expression of α4βδ γ-amino-butyric acid-A (GABAA) receptors (GABARs) in CA1 hippocampus. These receptors, which normally have low expression in this central nervous system (CNS) site, emerge along the apical dendrites as well as on the dendritic spines of pyramidal neurons, adjacent to excitatory synapses where they underlie a tonic inhibition that shunts excitatory current and impairs activation of N-methyl-D-aspartate (NMDA) receptors, the trigger for synaptic plasticity. As would be expected, α4βδ expression at puberty also prevents long-term potentiation (LTP), an in vitro model of learning which is a function of network activity, induced by theta burst stimulation of the Schaffer collaterals to the CA1 hippocampus. The expression of these receptors also impairs spatial learning in a hippocampal-dependent task. These impairments are not seen in δ knock-out (−/−) mice, implicating α4βδ GABARs. α4βδ GABARs are also a sensitive target for steroids such as THP ([allo]pregnanolone or 3α-OH-5α[β]-pregnan-20-one), which are dependent upon the polarity of GABAergic current. It is well-known that THP can increase depolarizing current gated by α4βδ GABARs, but more recent data suggest that THP can reduce hyperpolarizing current by accelerating receptor desensitization. At puberty, THP reduces the hyperpolarizing GABAergic current, which removes the shunting inhibition that impairs synaptic plasticity and learning at this time. However, THP, a stress steroid, also increases anxiety, via its action at α4βδ GABARs because it is not seen in δ−/− mice. These findings will be discussed as well as their relevance to changes in mood and cognition at puberty, which can be a critical period for certain types of learning and when anxiety disorders and mood swings can emerge.

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Acute Ethanol Administration and Acute Allopregnanolone Administration Impair Spatial Memory in the Morris Water Task

Cited by 107 publications

References 51 publications

The effects of acute and chronic ethanol exposure on presynaptic and postsynaptic gamma-aminobutyric acid (GABA) neurotransmission in cultured cortical and hippocampal neurons

The effects of acute and chronic ethanol exposure on presynaptic and postsynaptic gamma-aminobutyric acid (GABA) neurotransmission in cultured cortical and hippocampal neurons

The role of GABAA receptors in the acute and chronic effects of ethanol: a decade of progress

α4βδ GABAA receptors and tonic inhibitory current during adolescence: effects on mood and synaptic plasticity

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