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Dive into the research topics where Melisa J. Wallace is active.

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Featured researches published by Melisa J. Wallace.


European Journal of Pharmacology | 2001

Assessment of the role of CB1 receptors in cannabinoid anticonvulsant effects

Melisa J. Wallace; Jenny L. Wiley; Billy R. Martin; Robert J. DeLorenzo

The cannabinoid CB1 receptor has been shown to be the primary site of action for cannabinoid-induced effects on the central nervous system. Activation of this receptor has proven to dampen neurotransmission and produce an overall reduction in neuronal excitability. Cannabinoid compounds like delta9-tetrahydrocannabinol and cannabidiol have been shown to be anticonvulsant in maximal electroshock, a model of partial seizure with secondary generalization. However, until now, it was unknown if these anticonvulsant effects are mediated by the cannabinoid CB1 receptor. Likewise, (R)-(+)-[2,3-Dihydro-5-methyl-3-(4-morpholinylmethyl)pyrrolo[1,2,3-de]-1,4-benzoxazin-6-yl]-1-naphthalenylmethanone (WIN 55,212-2), a cannabimimetic compound that has been shown to decrease hyperexcitability in cell culture models via the cannabinoid CB1 receptor, has never been evaluated for anticonvulsant activity in an animal seizure model. We first show that the cannabinoid compounds delta9-tetrahydrocannabinol (ED50 = 42 mg/kg), cannabidiol (ED50 = 80 mg/kg), and WIN 55,212-2 (ED50 = 47 mg/kg) are anticonvulsant in maximal electroshock. We further establish, using the cannabinoid CB1 receptor specific antagonist N-(piperidin-1-yl-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamidehydrochloride (SR141716A) (AD50 = 2.5 mg/kg), that the anticonvulsant effects of delta9-tetrahydrocannabinol and WIN 55,212-2 are cannabinoid CB1 receptor-mediated while the anticonvulsant activity of cannabidiol is not. This study establishes a role for the cannabinoid CB1 receptor in modulating seizure activity in a whole animal model.


Journal of Biological Chemistry | 2007

Protein Kinase Cϵ Regulates γ-Aminobutyrate Type A Receptor Sensitivity to Ethanol and Benzodiazepines through Phosphorylation of γ2 Subunits

Zhan Heng Qi; Maengseok Song; Melisa J. Wallace; Dan Wang; Philip M. Newton; Thomas McMahon; Wen-Hai Chou; Chao Zhang; Kevan M. Shokat; Robert O. Messing

Ethanol enhances γ-aminobutyrate (GABA) signaling in the brain, but its actions are inconsistent at GABAA receptors, especially at low concentrations achieved during social drinking. We postulated that the ϵ isoform of protein kinase C (PKCϵ) regulates the ethanol sensitivity of GABAA receptors, as mice lacking PKCϵ show an increased behavioral response to ethanol. Here we developed an ATP analog-sensitive PKCϵ mutant to selectively inhibit the catalytic activity of PKCϵ. We used this mutant and PKCϵ-/- mice to determine that PKCϵ phosphorylates γ2 subunits at serine 327 and that reduced phosphorylation of this site enhances the actions of ethanol and benzodiazepines at α1β2γ2 receptors, which is the most abundant GABAA receptor subtype in the brain. Our findings indicate that PKCϵ phosphorylation of γ2 regulates the response of GABAA receptors to specific allosteric modulators, and, in particular, PKCϵ inhibition renders these receptors sensitive to low intoxicating concentrations of ethanol.


The Journal of Neuroscience | 2004

Deletion of N-type calcium channels alters ethanol reward and reduces ethanol consumption in mice

Philip M. Newton; Christine J. Orr; Melisa J. Wallace; Chanki Kim; Hee Sup Shin; Robert O. Messing

N-type calcium channels are modulated by acute and chronic ethanol exposure in vitro at concentrations known to affect humans, but it is not known whether N-type channels are important for behavioral responses to ethanol in vivo. Here, we show that in mice lacking functional N-type calcium channels, voluntary ethanol consumption is reduced and place preference is developed only at a low dose of ethanol. The hypnotic effects of ethanol are also substantially diminished, whereas ethanol-induced ataxia is mildly increased. These results demonstrate that N-type calcium channels modulate acute responses to ethanol and are important mediators of ethanol reward and preference.


Genes, Brain and Behavior | 2009

Amygdala protein kinase C epsilon controls alcohol consumption

Heidi M. B. Lesscher; Melisa J. Wallace; Lily Zeng; Victoria Wang; J. K. Deitchman; Thomas McMahon; Robert O. Messing; Philip M. Newton

Alcoholism is a progressive disorder that involves the amygdala. Mice lacking protein kinase C epsilon (PKCɛ) show reduced ethanol consumption, sensitivity and reward. We therefore investigated whether PKCɛ signaling in the amygdala is involved in ethanol consumption. Local knockdown of PKCɛ in the amygdala reduced ethanol consumption and preference in a limited‐access paradigm. Further, mice that are heterozygous for the PKCɛ allele consume less ethanol compared with wild‐type mice in this paradigm. These mice have a >50% reduction in the abundance of PKCɛ in the amygdala compared with wild‐type mice. We conclude that amygdala PKCɛ is important for ethanol consumption in mice.


Neuropsychopharmacology | 2007

Acute Functional Tolerance to Ethanol Mediated by Protein Kinase Cɛ

Melisa J. Wallace; Philip M. Newton; Miho Oyasu; Thomas McMahon; Wen-Hai Chou; Jacklyn Connolly; Robert O. Messing

A low level of response to ethanol is associated with increased risk of alcoholism. A major determinant of the level of response is the capacity to develop acute functional tolerance (AFT) to ethanol during a single drinking session. Mice lacking protein kinase C epsilon (PKCɛ) show increased signs of ethanol intoxication and reduced ethanol self-administration. Here, we report that AFT to the motor-impairing effects of ethanol is reduced in PKCɛ (−/−) mice when compared with wild-type littermates. In wild-type mice, in vivo ethanol exposure produced AFT that was accompanied by increased phosphorylation of PKCɛ and resistance of GABAA receptors to ethanol. In contrast, in PKCɛ (−/−) mice, GABAA receptor sensitivity to ethanol was unaltered by acute in vivo ethanol exposure. Both PKCɛ (−/−) and PKCɛ (+/+) mice developed robust chronic tolerance to ethanol, but the presence of chronic tolerance did not change ethanol preference drinking. These findings suggest that ethanol activates a PKCɛ signaling pathway that contributes to GABAA receptor resistance to ethanol and to AFT. AFT can be genetically dissociated from chronic tolerance, which is not regulated by PKCɛ and does not alter PKCɛ modulation of ethanol preference.


Genes, Brain and Behavior | 2007

Increased response to morphine in mice lacking protein kinase C epsilon

Philip M. Newton; Joseph A. Kim; A. J. McGeehan; J. P. Paredes; Kathleen Chu; Melisa J. Wallace; Amanda J. Roberts; Clyde W. Hodge; Robert O. Messing

The protein kinase C (PKC) family of serine–threonine kinases has been implicated in behavioral responses to opiates, but little is known about the individual PKC isozymes involved. Here, we show that mice lacking PKCɛ have increased sensitivity to the rewarding effects of morphine, revealed as the expression of place preference and intravenous self‐administration at very low doses of morphine that do not evoke place preference or self‐administration in wild‐type mice. The PKCɛ null mice also show prolonged maintenance of morphine place preference in response to repeated testing when compared with wild‐type mice. The supraspinal analgesic effects of morphine are enhanced in PKCɛ null mice, and the development of tolerance to the spinal analgesic effects of morphine is delayed. The density of μ‐opioid receptors and their coupling to G‐proteins are normal. These studies identify PKCɛ as a key regulator of opiate sensitivity in mice.


The Journal of Neuroscience | 2008

A Blocker of N- and T-type Voltage-Gated Calcium Channels Attenuates Ethanol-Induced Intoxication, Place Preference, Self-Administration, and Reinstatement

Philip M. Newton; Lily Zeng; Victoria Wang; Jacklyn Connolly; Melisa J. Wallace; Chanki Kim; Hee-Sup Shin; Francesco Belardetti; Terrance P. Snutch; Robert O. Messing

There is a clear need for new therapeutics to treat alcoholism. Here, we test our hypothesis that selective inhibitors of neuronal calcium channels will reduce ethanol consumption and intoxication, based on our previous studies using knock-out mice and cell culture systems. We demonstrate that pretreatment with the novel mixed N-type and T-type calcium channel antagonist 1-(6,6-bis(4-fluorophenyl)hexyl)-4-(3,4,5-trimethoxybenzyl)piperazine (NP078585) reduced ethanol intoxication. NP078585 also attenuated the reinforcing and rewarding properties of ethanol, measured by operant self-administration and the expression of an ethanol conditioned place preference, and abolished stress-induced reinstatement of ethanol seeking. NP078585 did not affect alcohol responses in mice lacking N-type calcium channels. These results suggest that selective calcium channel inhibitors may be useful in reducing acute ethanol intoxication and alcohol consumption by human alcoholics.


Neurotoxicology and Teratology | 1997

Perinatal Methadone Exposure Affects Dopamine, Norepinephrine, and Serotonin in the Weanling Rat

Susan E. Robinson; Jennifer R. Maher; Melisa J. Wallace; Paul M. Kunko

On gestational day 7 pregnant rats were implanted with osmotic minipumps containing either methadone hydrochloride (initial dose, 9 mg/kg/day) or sterile water. Their offspring were cross-fostered so that they were exposed to methadone prenatally and/or postnatally. On postnatal day 21, dopamine (DA), norepinephrine (NE), serotonin (5-HT), and their metabolites were analyzed. Perinatal methadone exposure disrupted dopaminergic, noradrenergic, and serotonergic activity in a brain region- and gender-specific fashion. The ratio of the DA metabolite 3,4-dihydroxyphenylacetic acid (DOPAC) to DA was reduced in the frontal cortex of males exposed to methadone postnatally. No effects of perinatal methadone exposure were observed on DA and DOPAC in the striatum. The ratio of 3-methoxy-4-hydroxyphenylglycol (MOPEG) to NE in the hippocampus was increased significantly in males exposed to methadone prenatally. Striatal and parietal cortical 5-hydroxyindoleacetic acid (5-HIAA), but not its ratio to 5-HT, was increased slightly in rats exposed to methadone postnatally. Although parietal cortical 5-HT, 5-HIAA, and 5-hydroxytryptophan were all affected by perinatal methadone exposure, the ratios of metabolite and precursor to 5-HT were not affected. Effects of methadone exposure appeared to depend upon the developmental stage at which exposure occurred and did not appear to result from the phenomenon of neonatal withdrawal. Changes in activity of these three neurotransmitter systems may contribute to the effect of perinatal methadone on the activity of other neurons, such as cholinergic neurons.


Educational Studies | 2014

Turnaround time and market capacity in contract cheating

Melisa J. Wallace; Philip M. Newton

Contract cheating is the process whereby students auction off the opportunity for others to complete assignments for them. It is an apparently widespread yet under-researched problem. One suggested strategy to prevent contract cheating is to shorten the turnaround time between the release of assignment details and the submission date, thus making it difficult for students to make arrangements with contractors. Here, we outline some characteristics of the current market for contract cheating and demonstrate that short turnaround times are unlikely to prevent contract cheating because requested turnaround times for university-level assignments completed via contract cheating are already short (average 5 days). In addition, for every contractor awarded a job, there are an average of 10 others offering to complete it within the specified time suggesting that there is abundant excess capacity in the market.


European Journal of Pharmacology | 1997

Extracellular aspartate concentration increases in nucleus accumbens after cocaine sensitization

Susan E. Robinson; Paul M. Kunko; Jason A. Smith; Melisa J. Wallace; Qiu Mo; Jennifer R. Maher

Rats were sensitized to cocaine (15 mg/kg, i.p.) by 6 daily injections followed by a 48 h withdrawal prior to cocaine challenge. Involvement of excitatory amino acids in behavioral sensitization was assessed by comparing extracellular levels of aspartate and glutamate in the core of the nucleus accumbens in response to the first cocaine injection and the final cocaine challenge. Intracerebral microdialysis of the nucleus accumbens in freely moving awake rats allowed the comparison of behavioral state with extracellular aspartate and glutamate concentrations. Increased nucleus accumbens extracellular concentration of aspartate, but not glutamate, was observed in rats exhibiting behavioral sensitization to cocaine.

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Susan E. Robinson

Virginia Commonwealth University

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Robert O. Messing

University of Texas at Austin

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Thomas McMahon

University of California

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Billy R. Martin

Virginia Commonwealth University

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Wen-Hai Chou

University of California

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