Browsing by Subject "quinine"

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    The ACT Malaria Treatment Policy Change in Kenya
    (Association of Kenya Physicians, 2007) Akhwale, Willis S.; Association of Kenya Physicians Scientific Conference (11th : Mar. 2007 : Eldoret, Kenya)
    Objectives of the national Antimalarial treatment policy: •Enable population at risk access safe, good quality, effective, affordable & acceptable antimalarial drugs •Ensure rapid and long lasting clinical cure •Prevent progression to severe disease •Reduce the incidence of anaemia •Reduce consequences of placental malaria infection •Delay development of resistance to antimalarial drugs Key specific issues: •Limited data available on safety of ACTs in young infants (use of coartem <5kgs) •Lack of adequate safety and efficacy data on drug combinations in pregnant women (safety of lumefantrine in pregnancy) •Improving systems of forecasting of drug needs •Strengthening the management and drug supply system (procurement, distribution and use) according to the specificities of the new drugs (shorter shelf life and the course-of-therapy packs) •Complex treatment schedules poses challenge for ensuring compliance •Need for more friendly paediatric formulations
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    Crossed high alcohol preferring mice exhibit aversion-resistant responding for alcohol with quinine but not footshock punishment
    (Elsevier, 2022-12) Sneddon, Elizabeth A.; Schuh, Kristen M.; Fennell, Kaila A.; Grahame, Nicholas J.; Radke, Anna K.; Psychology, School of Science
    A symptom of alcohol use disorder (AUD) is compulsive drinking, or drinking that persists despite negative consequences. In mice, aversion-resistant models are used to model compulsive-like drinking by pairing the response for alcohol with a footshock or by adding quinine, a bitter tastant, to the alcohol solution. crossed High Alcohol Preferring (cHAP) mice, a selectively bred line of mice that consumes pharmacologically relevant levels of alcohol, demonstrate a high level of aversion-resistance to quinine-adulterated alcohol. The current study investigated quinine-resistant and footshock-resistant responding for 10% ethanol in male and female cHAP mice with vs. without a history of alcohol exposure. cHAP mice were first trained to respond for 10% ethanol in an operant-response task. Next, mice were exposed to water or 10% ethanol for twelve 24-h sessions using a two-bottle choice procedure. Footshock-resistant ethanol responding was then tested in the operant chamber by pairing a footshock (0.35 mA) with the nose-poke response during one session. Quinine-resistant responding for alcohol was tested over five sessions (500–2500 μM quinine). Finally, footshock sensitivity was assessed using a flinch, jump, vocalize test. Alcohol exposure history did not influence responses for 10% ethanol or either measure of aversion-resistance. Further, cHAP mice were sensitive to footshock punishment but continued to respond for alcohol at all quinine concentrations. No sex differences were observed in any measure of alcohol responding, but female cHAP mice were less sensitive to footshock than males. These results replicate and extend the previous demonstration of a robust, innate resistance to quinine aversion in cHAP mice and further suggest that this tendency is not observed when footshock is used to punish drinking.
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    Role of the Prefrontal Cortex to Dorsomedial Striatum Projections in Compulsive Alcohol Drinking
    (2023-12) Bauer, Meredith; Boehm, Stephen; Lapish, Christopher; Grahame, Nicholas; Gremel, Christina
    Compulsive alcohol drinking is a defining feature of alcohol use disorder and is characterized as drinking alcohol despite knowledge of negative consequences. This behavior is hypothesized to be due to a disruption in the decision-making process. Decision making relies on a balance between goal-directedness and habit systems to efficiently execute behavior. An important distinction between compulsive and non-compulsive individuals is the ability to withhold drinking in the face of a negative consequence. The dorsomedial striatum (DMS) and dorsomedial prefrontal cortex (dmPFC) are brain regions necessary for goal directed behavior where the dmPFC is important for cognitive control and behavioral inhibition while the DMS is important for action selection. Importantly, the dmPFC sends a glutamatergic input to the DMS. We hypothesize this input is a behavioral control which is necessary to withhold action selection. Thus, in order to maintain non-compulsive alcohol use, the dmPFC and DMS need to work together to orchestrate inhibition of action selection in the face of negative consequences. Previous research shows a causal role for both the dmPFC and DMS in preventing compulsive alcohol drinking and a role for the projections from the dmPFC to DMS in behavioral inhibition. However, no research has demonstrated a role for this circuit’s activity in prevention of compulsive alcohol use. The current experiment tested the hypothesis that inhibiting the glutamatergic projection from the dmPFC to the DMS will cause non-compulsive Wistar rats to drink alcohol compulsively.