ABSTRACT
Systemic manipulations that enhance dopamine (DA) transmission around the time of fear extinction can strengthen fear extinction and reduce conditioned fear relapse. Prior studies investigating the brain regions where DA augments fear extinction focus on targets of mesolimbic and mesocortical DA systems originating in the ventral tegmental area, given the role of these DA neurons in prediction error. The dorsal striatum (DS), a primary target of the nigrostriatal DA system originating in the substantia nigra (SN), is implicated in behaviors beyond its canonical role in movement, such as reward and punishment, goal-directed action, and stimulus-response associations, but whether DS DA contributes to fear extinction is unknown. We have observed that chemogenetic stimulation of SN DA neurons during fear extinction prevents the return of fear in contexts different from the extinction context, a form of relapse called renewal. This effect of SN DA stimulation is mimicked by a DA D1 receptor (D1R) agonist injected into the DS, thus implicating DS DA in fear extinction. Different DS subregions subserve unique functions of the DS, but it is unclear where in the DS D1R agonist acts during fear extinction to reduce renewal. Furthermore, although fear extinction increases neural activity in DS subregions, whether neural activity in DS subregions is causally involved in fear extinction is unknown. To explore the role of DS subregions in fear extinction, adult, male Long-Evans rats received microinjections of either the D1R agonist SKF38393 or a cocktail consisting of GABAA/GABAB receptor agonists muscimol/baclofen selectively into either dorsomedial (DMS) or dorsolateral (DLS) DS subregions immediately prior to fear extinction, and extinction retention and renewal were subsequently assessed drug-free. While increasing D1R signaling in the DMS during fear extinction did not impact fear extinction retention or renewal, DMS inactivation reduced later renewal. In contrast, DLS inactivation had no effect on fear extinction retention or renewal but increasing D1R signaling in the DLS during extinction reduced fear renewal. These data suggest that DMS and DLS activity during fear extinction can have opposing effects on later fear renewal, with the DMS promoting renewal and the DLS opposing renewal. Mechanisms through which the DS could influence the contextual gating of fear extinction are discussed.
Subject(s)
Corpus Striatum , Extinction, Psychological , Fear , Receptors, Dopamine D1 , Animals , Fear/physiology , Fear/drug effects , Extinction, Psychological/drug effects , Extinction, Psychological/physiology , Male , Rats , Corpus Striatum/drug effects , Corpus Striatum/physiology , Corpus Striatum/metabolism , Receptors, Dopamine D1/physiology , Receptors, Dopamine D1/metabolism , Receptors, Dopamine D1/antagonists & inhibitors , Dopamine Agonists/pharmacology , Conditioning, Classical/drug effects , Conditioning, Classical/physiology , Dopaminergic Neurons/drug effects , Dopaminergic Neurons/physiology , Substantia Nigra/drug effects , Substantia Nigra/physiology , Rats, Long-Evans , Dopamine/metabolism , Dopamine/physiologyABSTRACT
The study was done to know whether the powders of Phyllanthus amarus plants favourably influence the duration of disease in patients with acute viraus B hepatitis when compared to placebo. The powders of the plant were given in capsule form (300 mg capsules--3 capsules--3 capsules thrice daily) and an antacid powder in similar capsule was used as placebo. Persons with encephalopathy, preexisting medical conditions or serum bilirubin above 350 iu/l were excluded from the study. Fifty seven patients were randomized to receive either the placebo (28 cases) or the drug (28 cases). The two groups were comparable at the time of entry. Two cases from the placebo and one from the placebo and one from the drug group dropped out of the study. The duration of disease (time taken for bilirubin to come to below 2 mg%) was taken as the outcome measure. The duration of disease in the two groups was compared by Cox's proportional hazards analysis after adusting for the variables that influence the duration of jaundice. Only initial serum bilirubin was an independent predictor of duration of jaundice. The an analysis showed that Phyllanthus amarus powders did not significantly reduce the duration of jaundice in persons with virus B hepatitis.
Subject(s)
Antiviral Agents/therapeutic use , Euphorbiaceae/therapeutic use , Hepatitis B/therapy , Phytotherapy , Acute Disease , Adult , Double-Blind Method , Female , Humans , Male , Treatment OutcomeABSTRACT
Effect of feeding safflower oil and coconut oil in experimental myocardial infarction induced by isoproterenol in rats was studied. Based on the survival rate and histopathological examination, safflower oil was found to offer better protection than coconut oil. Serum GOT levels also confirmed the protective activity of safflower oil. The concentrations of cholesterol and triglycerides in the heart and aorta were lower in the safflower oil fed group, while the level of phospholipids was higher.
Subject(s)
Cocos , Dietary Fats/pharmacology , Lipids/analysis , Myocardial Infarction/blood , Plant Oils/pharmacology , Safflower Oil/pharmacology , Animals , Aorta/chemistry , Coconut Oil , Isoproterenol , Male , Myocardial Infarction/chemically induced , Myocardium/chemistry , RatsABSTRACT
Effect of ethanol administration on the severity of myocardial infarction induced by isoproterenol in rats was studied. Even though serum CPK and GOT levels as well as the extent of myocardial damage as revealed by histopathological studies, were similar, the survival rate was higher in rats administered ethanol. Concentration of cholesterol and triglycerides in the serum and heart in rats given ethanol and isoproterenol seems to be the additive effect caused individually by ethanol and isoproterenol. Myocardial alcohol dehydrogenase and aldehyde dehydrogenase both showed increased activity in rats treated with ethanol. The rate of recovery from myocardial infarction however, was slower in rats treated with ethanol as judged from the serum CPK value.
