Phenobarbital pre-treatment prevents kainic acid-induced impairments in acquisition learning.
Animal/drug effects; Animals; Behavior; Cues; Excitatory Amino Acid Agonists/*toxicity; GABA Modulators/*pharmacology; Kainic Acid/*antagonists & inhibitors/*toxicity; Learning/drug effects; Long-Evans; Male; Maze Learning/*drug effects; Memory/drug effects; Phenobarbital/*pharmacology; Rats; Seizures/chemically induced/prevention & control
This study examined the protective effect of phenobarbital on kainic acid-induced deficits in acquisition learning. A single kainic acid injection (9 mg/kg i.p.) was administered five days prior to testing using the Morris water maze test. Kainic acid produced deficits in the acquisition of spatial information observed as an increase in latency to a hidden escape platform. Daily phenobarbital treatment (20 mg/kg i.p.) initiated 45 minutes prior to the kainic acid injection blocked the kainic acid-induced deficits in acquisition learning. When daily phenobarbital treatment was initiated 2-3 hours after kainic acid seizure development it did not block the kainic acid induced-deficits in water maze performance. Daily administration of phenobarbital alone at the moderate concentration used in this study did not cause alterations in behavioral performance in the Morris water maze. These studies indicate that phenobarbital pre-treatment results in a behavioral neuroprotection against kainic acid-induced neurotoxicity.
Brown-Croyts L M; Caton P W; Radecki D T; McPherson S L
Life sciences
2000
2000-06
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1016/s0024-3205(00)00658-5" target="_blank" rel="noreferrer noopener">10.1016/s0024-3205(00)00658-5</a>
Sex differences in dopamine- and vesicular monoamine-transporter functions.
3; 4-Dihydroxyphenylacetic Acid/metabolism; Adrenergic Uptake Inhibitors/metabolism; Animal/drug effects; Animals; Behavior; Behavior/drug effects; Corpus Striatum/metabolism; Dopamine Agents/pharmacology; Dopamine Plasma Membrane Transport Proteins/*metabolism; Dopamine Uptake Inhibitors/metabolism; Female; Humans; Male; Methamphetamine/pharmacology; Mice; Nomifensine/metabolism; Reserpine/metabolism; Sex Factors; Vesicular Monoamine Transport Proteins/*metabolism
Men and women differ with regard to their use of, and responses to, methamphetamine (MA). Analogous sex differences with regard to MA are observed in animal models. In this report, data from a series of experiments that focus upon dopamine transporter (DAT) and vesicular monoamine transporter2 (VMAT2) function are reviewed by way of providing some understanding for these sex differences to MA. The amount of dopamine (DA) recovered after infusion of DA into superfused striatal tissue was greater in females and an accentuated amount of extracellular DA was obtained from females after infusion of the DAT-blocking drug, nomifensine. These data suggest a higher level of DAT activity in females. To evaluate the implications of this sex difference in DAT function as related to MA, the amount of DA evoked by an infusion of MA into superfused striatal tissue was tested and found to be significantly greater in males. In contrast, potassium chloride-stimulated DA release was greater in females. The results of these
Dluzen D E; McDermott J L
Annals of the New York Academy of Sciences
2008
2008-10
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1196/annals.1432.010" target="_blank" rel="noreferrer noopener">10.1196/annals.1432.010</a>
Chemopreventive doses of resveratrol do not produce cardiotoxicity in a rodent model of hepatocellular carcinoma.
*Chemoprevention; Analysis of Variance; Animal; Animal Studies; Animal/drug effects; Animals; Antioxidants; Behavior; Blotting; Carcinoma; Cardiotoxicity; Cardiotoxins/*toxicity; Chemoprevention; Data Analysis Software; Descriptive Statistics; Disease Models; Doppler; Dose-Response Relationship; Drug; Echocardiography; Feeding Behavior/drug effects; Female; Fisher's Exact Test; Funding Source; Heart – Drug Effects; Heart/drug effects/physiopathology; Hepatocellular – Prevention and Control; Hepatocellular/*drug therapy/pathology/physiopathology; Hepatocytes/drug effects/pathology; Humans; Liver Neoplasms/*drug therapy/pathology/physiopathology; Liver/drug effects/pathology/physiopathology; Polyphenols – Therapeutic Use; Rats; Resveratrol; Sprague-Dawley; Stilbenes/*therapeutic use; Systole/drug effects; Western
Hepatocellular carcinoma (HCC), one of the most lethal cancers, results in more than one million fatalities worldwide every year. In view of the limited therapeutic alternatives and poor prognosis of liver cancer, preventive control approaches, notably chemoprevention, have been considered to be the best strategy in lowering the present prevalence of the disease. Resveratrol, a naturally occurring antioxidant and antiinflammatory agent found in grapes and red wine, inhibits carcinogenesis with a pleiotropic mode of action. Recently, we have reported that dietary resveratrol significantly prevents chemically-induced liver tumorigenesis in rats. One of the mechanisms of resveratrol-mediated chemoprevention of hepatocarcinogenesis could be related to its antiinflammatory action through hepatic cyclooxygenase (COX-2) inhibition. Although several COX-2 inhibitors are known to exert chemopreventive efficacy, not all are considered ideal candidates for chemoprevention due to the risk of adverse cardiovascular events. Accordingly, the objective of the present study was to evaluate the role of resveratrol on cardiac performance during experimental hepatocarcinogenesis initiated with diethylnitrosamine and promoted by phenobarbital. Rats had free access to diet supplemented with resveratrol four weeks before the carcinogen injection and 14 weeks thereafter. The cardiotoxicity of resveratrol was assessed by monitoring the cardiac function using transthoracic echocardiography as well as Western blot analysis of cardiac tissue. Long-term dietary administration of resveratrol dose-dependently suppressed hepatic tumor multiplicity, the principal endpoint for evaluating the chemopreventive potential of a candidate agent. The chemopreventive effects of resveratrol were also reflected in histopathological assessment of hepatic tissues. Resveratrol did not exhibit any cardiotoxicity but rather improved the cardiac function in a dose-responsive fashion. Our results indicate that resveratrol-mediated chemoprevention of rat liver carcinogenesis is devoid of any adverse cardiovascular events. Resveratrol may be developed as a chemopreventive as well as therapeutic drug for human HCC.
Luther Daniel J; Ohanyan Vahagn; Shamhart Patricia E; Hodnichak Cheryl M; Sisakian Hamayak; Booth Tristan D; Meszaros J Gary; Bishayee Anupam
Investigational new drugs
2011
2011-04
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1007/s10637-009-9332-7" target="_blank" rel="noreferrer noopener">10.1007/s10637-009-9332-7</a>
Interaction of ethanol and tetrahydro-beta-carboline (THBC) in a discriminative task.
Male; Animals; Rats; Ethanol/*pharmacology; Behavior; Drug Interactions; Discrimination Learning/*drug effects; Conditioning (Psychology)/drug effects; Carbolines/*pharmacology; Dose-Response Relationship; Drug; Inbred Strains; Animal/drug effects
Rats (n = 10) were trained to discriminate between ethanol (600 mg/kg, IP) and its vehicle, or between THBC (20 mg/kg) and its vehicle in a two-lever food-motivated operant task. Once the discriminative training criterion was attained, rats in each group were administered different doses of both ethanol and THBC. The ED50 of ethanol in the ethanol-trained rats was 298.0 mg/kg and 15 mg/kg THBC produced ethanol-like responding. The ED50 of THBC in the THBC-trained rats was 3.63 mg/kg and 1200 mg/kg ethanol produced THBC-like responding. The cross-generalization between ethanol and THBC is, thus, indicated and relates to previous evidence in which both ethanol- and THBC-trained rats generalize to a common agent, TFMPP, a putatively specific 5HT1B receptor agonist. Taken together, these observations suggest that beta-carbolines may play a role in the discriminative stimulus properties of ethanol.
Schechter M D; Signs S A
Alcohol (Fayetteville, N.Y.)
1988
1988-08
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1016/0741-8329(88)90075-4" target="_blank" rel="noreferrer noopener">10.1016/0741-8329(88)90075-4</a>