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Brian A. McMillen

Bio: Brian A. McMillen is an academic researcher from East Carolina University. The author has contributed to research in topics: Alcohol abuse & Addiction. The author has an hindex of 25, co-authored 72 publications receiving 1600 citations.


Papers
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Journal ArticleDOI
TL;DR: Differences in storage and releasable pools of dopamine and norepinephrine should be taken into account when comparing the pharmacology of these 2 monaminergic neuronal systems.

199 citations

Journal ArticleDOI
TL;DR: Gepirone may be a weak postsynaptic 5HT agonist, but its primary effect is to decrease 5HT neurotransmission, in harmony with reports that decreased serotonergic activity has anxiolytic-like effects in animal models of anxiety.
Abstract: Gepirone (BMY 13805), a buspirone analog, was used to determine the antianxiety mechanism of the arylpiperazine class of drugs. Because of the weak effects of these drugs on conflict behavior, isolation-induced aggressive mice were used as the antianxiety model. Gepirone, like buspirone, potently inhibited attacks against group housed intruder mice (ED50 = 4.5 mg/kg i.p.) without causing sedation or ataxia. Inhibition of aggression was potentiated by co-administration of 0.25 mg/kg methiothepin or 2.5 mg/kg methysergide. Gepirone had variable effects on dopamine metabolism and reduced 5-hydroxytryptamine (5HT) metabolism about one third after a dose of 2.5 mg/kg. In contrast to buspirone, which markedly increased dopaminergic impulse flow, gepirone inhibited the firing of most cells recorded from the substantia nigra zona compacta in doses of 2.3-10 mg/kg i.v. and the effects were reversible by administration of haloperidol. The common metabolite of buspirone and gepirone, 1-(2-pyrimidinyl)-piperazine, caused increased firing rates only. Gepirone potently inhibited serotonergic impulse flow recorded from the dorsal raphe nucleus (88.3% after 0.04 mg/kg) and this effect was partially reversed by serotonergic antagonists. Both buspirone and gepirone displaced [3H]-5HT from the 5HT1a binding site in the hippocampus with IC50 values of 10 and 58 nM, respectively. Non-alkyl substituted aryl-piperazines displaced [3H]-5HT from both 5HT1a and 5HT1b binding sites. Thus, although gepirone may be a weak postsynaptic 5HT agonist, its primary effect is to decrease 5HT neurotransmission. In support of this conclusion was the observed potentiation of antiaggressive effects by blocking 5HT receptors wit small doses of methiothepin or methysergide, which would exacerbate the decreased release of 5HT caused by gepirone. These results are in harmony with reports that decreased serotonergic activity has anxiolytic-like effects in animal models of anxiety.

80 citations

Journal ArticleDOI
TL;DR: It is demonstrated that cocaine exposure in utero at relevant doses can affect neonatal outcome and long term development in rat offspring.

80 citations

Journal ArticleDOI
TL;DR: The failure of the Cocaine-D animals to enter the open field is consistent with neophobic behavior that the authors have observed before in rats exposed in utero to cocaine.

77 citations

Journal ArticleDOI
TL;DR: The results suggest that few changes have occurred in monoaminergic receptor sensitivity as a result of the exposure to these drugs during gestation, and the behavioral changes that are known to occur following prenatal exposure to cocaine may be due to presynaptic alterations in neurotransmitter function rather than changes in postsynaptic receptors.

69 citations


Cited by
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Journal ArticleDOI
04 Sep 1987-Science
TL;DR: It is shown here that the potencies of cocaine-like drugs in self-administration studies correlate with their potencies in inhibiting [3H]mazindol binding to the dopamine transporters in the rat striatum, but not with theirPotencies in binding to a large number of other presynaptic and postsynaptic binding sites.
Abstract: Although cocaine binds to several sites in the brain, the biochemical receptor mechanism or mechanisms associated with its dependence producing properties are unknown. It is shown here that the potencies of cocaine-like drugs in self-administration studies correlate with their potencies in inhibiting [3H]mazindol binding to the dopamine transporters in the rat striatum, but not with their potencies in binding to a large number of other presynaptic and postsynaptic binding sites. Thus, the cocaine receptor related to substance abuse is proposed to be the one associated with dopamine uptake inhibition.

2,184 citations

Journal ArticleDOI
TL;DR: The enormous number of studies to be covered in this review prevented in‐depth discussion of many methodological, pharmacological or neurobiological aspects, so the presentation of data had to be limited to a short and condensed summary of the most relevant findings.
Abstract: Conditioned place preference (CPP) continues to be one of the most popular models to study the motivational effects of drugs and non-drug treatments in experimental animals. This is obvious from a steady year-to-year increase in the number of publications reporting the use this model. Since the compilation of the preceding review in 1998, more than 1000 new studies using place conditioning have been published, and the aim of the present review is to provide an overview of these recent publications. There are a number of trends and developments that are obvious in the literature of the last decade. First, as more and more knockout and transgenic animals become available, place conditioning is increasingly used to assess the motivational effects of drugs or non-drug rewards in genetically modified animals. Second, there is a still small but growing literature on the use of place conditioning to study the motivational aspects of pain, a field of pre-clinical research that has so far received little attention, because of the lack of appropriate animal models. Third, place conditioning continues to be widely used to study tolerance and sensitization to the rewarding effects of drugs induced by pre-treatment regimens. Fourth, extinction/reinstatement procedures in place conditioning are becoming increasingly popular. This interesting approach is thought to model certain aspects of relapse to addictive behavior and has previously almost exclusively been studied in drug self-administration paradigms. It has now also become established in the place conditioning literature and provides an additional and technically easy approach to this important phenomenon. The enormous number of studies to be covered in this review prevented in-depth discussion of many methodological, pharmacological or neurobiological aspects; to a large extent, the presentation of data had to be limited to a short and condensed summary of the most relevant findings.

1,265 citations

Book
11 Nov 2005
TL;DR: Theories of drug addiction: Transition from Neuroadaptation to Pathophysiology as mentioned in this paper Theories of Drug Addiction: Transitioning from NeuroAdaptation in Pathology to Pathology.
Abstract: 1. What is Addiction. 2. Animal Models of Drug Addiction. 3. Psychostimulants. 4. Opioids. 5. Alcohol. 6. Nicotine. 7. Cannabinoids. 8. Imaging. 9. Neurobiological Theories of Addiction. 10. Drug Addiction: Transition from Neuroadaptation to Pathophysiology.

813 citations

Journal ArticleDOI
TL;DR: A multitask strategy for modeling symptoms of autism will be useful for investigating targeted and random gene mutations, QTLs, and microarray analyses.

723 citations

Journal ArticleDOI
TL;DR: SR 141716, a selective central CB1 cannabinoid receptor antagonist, markedly and selectively reduces sucrose feeding and drinking as well as neuropeptide Y-induced sucrose drinking in rats.
Abstract: SR 141716, a selective central CB1 cannabinoid receptor antagonist, markedly and selectively reduces sucrose feeding and drinking as well as neuropeptide Y-induced sucrose drinking in rats. SR 141716 also decreases ethanol consumption in C57BL/6 mice. In contrast, blockade of CB1 receptors only marginally affects regular chow intake or water drinking. The active doses of SR 141716 (0.3-3 mg/kg) are in the range known to antagonize the characteristic effects induced by cannabinoid receptor agonists. These results suggest for the first time that endogenous cannabinoid systems may modulate the appetitive value of sucrose and ethanol, perhaps by affecting the activity of brain reward systems.

619 citations