Publications by authors named "ELLINWOOD E"

Diseases caused by ticks are often addressed as a traditional epidemiological mathematical puzzle, i.e., how many identical infected vectors, how many uniform potential hosts, and a dependable rate of transmission, etc.

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In traditional medicine, Panax ginseng has been used to treat various behavioral effects of psychostimulants (e.g., cocaine) and other drugs of abuse and to ameliorate withdrawal symptoms.

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Deprenyl, used clinically in Parkinson's disease, has multiple pharmacological effects which make it a good candidate to treat neurotoxicity. Thus, we investigated deprenyl's ability to attenuate methamphetamine-induced dopamine neurotoxicity. We also examined deprenyl's effect in changing markers associated with psychostimulant sensitization.

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We have previously found the 5-HT3 receptor antagonist ondansetron to be useful in reducing cocaine self-administration and cocaine induced sensitization in rats when given during cocaine withdrawal. More recently we have found the combination of the dopamine agonist pergolide plus ondansetron, 3.5 h later, to reverse cocaine sensitization and associated changes in NMDA and AMPA receptors.

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We have recently shown in rats that cocaine-induced behavioral sensitization can be reversed by a 5-day treatment with ondansetron given 3.5 h after daily pergolide injections. In this study we further investigated the molecular/neurochemical alterations underlying cocaine sensitization and pergolide/ondansetron-mediated reversal.

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The present study investigated whether GABA(A) receptor alpha2 subunit and GAD(67) are involved in chronic high dose methamphetamine (METH)-induced sensitization and neurotoxicity. The METH sensitization was established in rats by 7-day pump infusion plus daily injection (25mg/kg/day) and a subsequent 28-day withdrawal period. Behavioral sensitization was assessed by behavioral ratings after challenge with METH (0.

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Cocaine abusers remain vulnerable to drug craving and relapse for many years after abstinence is achieved. We have recently shown that ondansetron (a 5-HT3 receptor antagonist) given 3.5 h after each daily cocaine injection reverses previously established behavioral sensitization.

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Phosphatidylinositol 3-kinase (PI3K) is an important signaling molecule involved in cell differentiation, proliferation, survival, and phagocytosis, and may participate in various brain functions. To determine whether it is also involved in cocaine sensitization, we measured the p85alpha/p110 PI3K activity in the nuclear accumbens (NAc) shell, NAc core, and prefrontal cortex (PFC) following establishment of cocaine sensitization and its subsequent reversal. Naïve rats were rank-ordered and split into either daily cocaine or saline pretreatment group based on their locomotor responses to an acute cocaine injection (7.

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We compared two different methamphetamine dosing regimens and found distinct long-term behavioral and neurochemical changes. Adult rats were treated with 1-day methamphetamine injection (3x5 mg/kg s.c.

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We have previously shown that ondansetron, given 3.5 h after intravenous cocaine self-administration, can attenuate self-administration the following day. Here we tested ondansetron given either before or after a 14-h oral cocaine session in rats.

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We tested the tachykinin NK(1) receptor antagonist WIN51708 (17betahydroxy17alphaethynyl5alphaandrostanol[3,2b]pyrimido[1,2-a]benzimidazole) in a behavioral sensitization model. Rats were given 7 days of cocaine then 7 days of withdrawal to induce sensitization. Thereafter, another 7 days of cocaine with WIN51708 (2 mg/kg i.

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Male Sprague-Dawley rats were given two separate sensitizing regimens of cocaine (7 days on, 7 days off, 7 days on at 40 mg/kg/day, s.c.) or saline injections.

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Male Sprague-Dawley rats were given two separate sensitizing regimens of cocaine (7 days on, 7 days off, 7 days on; 40 mg/kg/day s.c.) along with saline controls.

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One therapeutic paradigm for cocaine abuse is a 24-h 'agonist' treatment which reduces reinforcing effects in a manner similar to the methadone maintenance model for heroin. However, 24-h dosing of dopamine (DA) agonists may induce side effects of insomnia and psychosis, as well as anergia and anhedonia which may actually potentiate abuse. Thus, it is important to determine the daily dose duration of potential treatments such as direct (e.

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Inhibition of endogenous dopamine release by photo-released dopamine (i.e., autoinhibition) was characterized in the rat caudate-putamen using combined caged-dopamine photolysis and fast-scan cyclic voltammetry.

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Cocaine dosing regimens in animals are used to model behavioral and neurochemical changes in human cocaine abusers. Typically, rats are dosed for 5-14 days and assessed at some point during withdrawal. However, human cocaine bingers undergo multiple periods of several days of abuse.

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Research into methamphetamine-induced neurotoxicity has experienced a resurgence in recent years. This is due to (1) greater understanding of the mechanisms underlying methamphetamine neurotoxicity, (2) its usefulness as a model for Parkinson's disease and (3) an increased abuse of the substance, especially in the American Mid-West and Japan. It is suggested that the commonly used experimental one-day methamphetamine dosing regimen better models the acute overdose pathologies seen in humans, whereas chronic models are needed to accurately model human long-term abuse.

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Using real-time voltammetry, we compared the effects of cocaine (1.0, 3.0, or 10 microM), WIN 35428 (0.

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To explore the significance of dopamine (DA) autoreceptors in cocaine tolerance and cocaine induced locomotor activity rats were treated with saline and cocaine (40 mg/kg per day via osmotic minipump; normal and cocaine tolerant rats, respectively). Injections of DS121 (0-7 mg/kg, i.p.

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Electrochemical measurements using voltammetry or amperometry at carbon-fiber microelectrodes have been used in vitro and in vivo to examine regulatory mechanisms for the central dopamine system. In many of these experiments, dopamine efflux concentrations under control conditions are determined followed by their alterations in response to a drug treatment. The present study demonstrates that some drugs can affect dopamine measurements, not only by their expected pharmacological action but also by directly altering the microelectrode responsivity.

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Intermittent cocaine administration induces sensitization (reverse tolerance) to its behavioral effects. The mechanism(s) mediating sensitization is not clear, however, previous research has implicated 5-HT(3) receptors in the expression of sensitization. The present experiment evaluated the ability of the 5-HT(3) receptor antagonist, ondansetron, administered during withdrawal from chronic intermittent cocaine administration, to block the expression of sensitization.

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Using slice preparations, we investigated the effects of chronic cocaine treatment on dopamine autoreceptor sensitivity in the nucleus accumbens core. Cocaine (40 mg/kg/day) was given for 14 days, either by continuous subcutaneous infusion (osmotic minipumps) or single daily injections. One or 7 days after cocaine withdrawal, we used fast scan cyclic voltammetry (10 Hz sampling rate) to measure inhibition of electrically evoked dopamine release by quinpirole (3-300 nM).

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The current experiment evaluated the dose-dependent nature of the induction of behavioral tolerance, and changes in dopamine autoreceptor function, by continuously administering different doses of cocaine. For all experiments, rats were exposed to a 14-day pretreatment regimen involving the continuous administration of either 0, 5, 10, 20, or 40 mg/kg/day cocaine. All subjects were then withdrawn from the pretreatment regimen for 7 days.

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Using in vivo single-unit recording in rats, we compared the effects of continuous cocaine infusion via minipump or single daily injections (both 40 mg/kg/d x 14 days, S.C.) on the activity of putative dopamine (DA) neurons in the substantia nigra pars compacta (SNC) and ventral tegmental area (VTA).

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We have previously reported that continuous cocaine administration functionally down regulates 5-HT3 receptors in the nucleus accumbens. The current experiments evaluated the duration of behavioral tolerance to cocaine and whether the duration of behavioral tolerance and 5-HT3 receptor down-regulation co-varied. Rats were withdrawn from a pretreatment regimen (40 mg/kg/per day cocaine or 0.

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