Browsing by Author "Leslie, Jacob"

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    Role of different subtypes of dopamine receptors in response to acute opiate withdrawal.
    (2011-01-06) Leslie, Jacob
    •Those experiencing withdrawal from drugs of abuse display negative emotional symptoms such as anxiety. Anxiety during withdrawal from an acute opiate exposure also causes potentiation of the acoustic startle reflex (“withdrawal-potentiated startle”).2,4,5 •Experiments in the Gewirtz lab with a general dopamine receptor agonist, apomorphine have suggested that anxiety during acute withdrawal from opioidsis mediated by levels of dopamine in the brain. •While we know dopamine is important in this phenomena we do not know which dopamine receptors play a role in producing anxiety symptoms. •There are five subtypes of dopamine subunits that are classified in two populations: D1-like and D2-like receptors. Both have been shown to play a role in producing withdrawal symptoms. 1,3 •Our goal is to discover which receptor family plays a role in producing withdrawal-potentiated startle. We will test this by administering either a D1-like agonist or D2-like agonist, or both in a cocktail with the expectation that withdrawal potentiated startle will be blocked in the groups that are important for producing anxiety.
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    Role of Dopamine in Anxiety Production During Acute Opiate Withdrawal
    (2012-04-18) Leslie, Jacob
    The use of addictive substances is characterized by a positive emotional state followed by drug withdrawal and a negative affective state. These highs and lows are caused by neuroadaptational changes in multiple brain structures when exposed to drugs of abuse. However, the neural events responsible for triggering the negative affective component of withdrawal during the early stages of morphine and nicotine dependence has yet to be definitively determined. By measuring the acoustic startle reflex in rats, we show that decreased dopaminergic activity causes the characteristic anxiety observed during withdrawal from drugs of abuse. These results parallel the substantial research showing the importance of the mesolimbic dopamine system in regulating the effects of drugs of abuse.
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    Roles of the BNST in Response to Acute Drug Withdrawal
    (2011-08-11) Leslie, Jacob
    •Those experiencing withdrawal from drugs of abuse display symptoms of dysphoria such as anxiety. Anxiety during withdrawal from an acute opiate exposure also causes potentiation of the acoustic startle reflex (“withdrawal-potentiated startle”).1,3,4 •The Gewirtz lab’s research has suggested that anxiety during acute withdrawal from opoids is mediated by levels of dopamine in the brain due to experiments with a general dopamine receptor agonist, apomorphine. Opiates disinhibit dopamenergic neurons in the VTA which project to the BNST and CeA. 2 •Withdrawal is hypothesized to be caused by the drop in dopamine levels in the brain. Apomorphine replaces dopamine at dopamine receptors and prevents withdrawal symptoms as measured by acoustic startle. •While we know dopamine is important in this phenomena we do not know which brain structures play a role in producing anxiety symptoms during withdrawal. •Our goal is to discover which brain structures play a role in producing withdrawal-potentiated startle. We will test this by administering apomorphine directly to the BNST, Bed Nucleus of the Stria Terminalis, after subcutaneous injection of morphine with the expectation that, if the BNST is critical for producing withdrawal potentiated startle, then withdrawal potentiated startle will be blocked .