Wolfman SL

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Full name : Wolfman Shannon L

First name : Shannon

Mail : University of Chicago Chicago IL 60637

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Country : USA

Email : shannon.wolfman@gmail.com

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References (4)

Title : Ethanol-Induced Motor Impairment Mediated by Inhibition of alpha7 Nicotinic Receptors - McDaid_2016_J.Neurosci_36_7768
Author(s) : McDaid J , Abburi C , Wolfman SL , Gallagher K , McGehee DS
Ref : Journal of Neuroscience , 36 :7768 , 2016
Abstract : Nicotine and ethanol (EtOH) are among the most widely co-abused substances, and nicotinic acetylcholine receptors (nAChRs) contribute to the behavioral effects of both drugs. Along with their role in addiction, nAChRs also contribute to motor control circuitry. The alpha7 nAChR subtype is highly expressed in the laterodorsal tegmental nucleus (LDTg), a brainstem cholinergic center that contributes to motor performance through its projections to thalamic motor relay centers, including the mediodorsal thalamus. We demonstrate that EtOH concentrations just above the legal limits for intoxication in humans can inhibit alpha7 nAChRs in LDTg neurons from rats. This EtOH-induced inhibition is mediated by a decrease in cAMP/PKA signaling. The alpha7 nAChR-positive allosteric modulator PNU120596 [N-(5-chloro-2,4-dimethoxyphenyl)-N'-(5-methyl-3-isoxazolyl)-urea], which interferes with receptor desensitization, completely eliminated EtOH modulation of these receptors. These data suggest that EtOH inhibits alpha7 responses through a PKA-dependent enhancement of receptor desensitization. EtOH also inhibited the effects of nicotine at presynaptic alpha7 nAChRs on glutamate terminals in the mediodorsal thalamus. In vivo administration of PNU120596 either into the cerebral ventricles or directly into the mediodorsal thalamus attenuated EtOH-induced motor impairment. Thus, alpha7 nAChRs are likely important mediators of the motor impairing effects of moderate EtOH consumption. SIGNIFICANCE STATEMENT: The motor-impairing effects of ethanol contribute to intoxication-related injury and death. Here we explore the cellular and neural circuit mechanisms underlying ethanol-induced motor impairment. Physiologically relevant concentrations of ethanol inhibit activity of a nicotinic receptor subtype that is expressed in brain areas associated with motor control. That receptor inhibition is mediated by decreased receptor phosphorylation, suggesting an indirect modulation of cell signaling pathways to achieve the physiological effects.
ESTHER : McDaid_2016_J.Neurosci_36_7768
PubMedSearch : McDaid_2016_J.Neurosci_36_7768
PubMedID: 27445152

Title : Tolerance to Ethanol or Nicotine Results in Increased Ethanol Self-Administration and Long-Term Depression in the Dorsolateral Striatum - Abburi_2016_eNeuro_3_
Author(s) : Abburi C , Wolfman SL , Metz RA , Kamber R , McGehee DS , McDaid J
Ref : eNeuro , 3 : , 2016
Abstract : Ethanol (EtOH) and nicotine are the most widely coabused drugs. Tolerance to EtOH intoxication, including motor impairment, results in greater EtOH consumption and may result in a greater likelihood of addiction. Previous studies suggest that cross-tolerance between EtOH and nicotine may contribute to the abuse potential of these drugs. Here we demonstrate that repeated intermittent administration of either EtOH or nicotine in adult male Sprague Dawley rats results in tolerance to EtOH-induced motor impairment and increased EtOH self-administration. These findings suggest that nicotine and EtOH cross-tolerance results in decreased aversive and enhanced rewarding effects of EtOH. Endocannabinoid signaling in the dorsolateral striatum (DLS) has been implicated in both EtOH tolerance and reward, so we investigated whether nicotine or EtOH pretreatment might modulate endocannabinoid signaling in this region. Using similar EtOH and nicotine pretreatment methods resulted in increased paired-pulse ratios of evoked EPSCs in enkephalin-positive medium spiny neurons in DLS slices. Thus, EtOH and nicotine pretreatment may modulate glutamatergic synapses in the DLS presynaptically. Bath application of the CB1 receptor agonist Win 55,2-212 increased the paired-pulse ratio of evoked EPSCs in control slices, while Win 55,2-212 had no effect on paired-pulse ratio in slices from either EtOH- or nicotine-pretreated rats. Consistent with these effects, nicotine pretreatment occluded LTD induction by high-frequency stimulation of the corticostriatal inputs to the dorsolateral striatum. These results suggest that nicotine and EtOH pretreatment modulates striatal synapses to induce tolerance to the motor-impairing effects of EtOH, which may contribute to nicotine and EtOH coabuse.
ESTHER : Abburi_2016_eNeuro_3_
PubMedSearch : Abburi_2016_eNeuro_3_
PubMedID: 27517088

Title : Poster: Cellular and synaptic mechanisms of nicotine aversion -
Author(s) : Wolfman SL , Gill DF , Bogdanic F , Al-Hasani R , McCall JG , Bruchas MR , McGehee DS
Ref : Biochemical Pharmacology , 97 :622 , 2015
PubMedID:

Title : Poster: Cellular and synaptic mechanisms of nicotine aversion -
Author(s) : Wolfman SL , Metz RAE , Hatz S , McGehee DS
Ref : Biochemical Pharmacology , 86 :1236 , 2013
PubMedID: