Modification of ethanol intoxication by dopamine agonists and antagonists

Bacopoulos, Nicholas G.; Bize, Isabel; Levine, Joyce N.; Orden, L. S. Van

doi:10.1007/bf00432293

Cited by 26 publications

(5 citation statements)

References 19 publications

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“…There is also evidence for dopaminergic involvement in various CNS effects of ethanol such as impairment of motor performance (Bacopoulos et al, 1979;Kiianmaa et al, 1979) and loss of the righting reflex (Erickson and Matchett, 1975). The corpus striatum was chosen because it is rich in DA and the system is relatively well understood.…”

Section: Introductionmentioning

confidence: 99%

The effect of acute ethanol on dopamine metabolism and other neurotransmitters in the hypothalamus and the corpus striatum of mice

Dar

Wooles

1984

J. Neural Transmission

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The effect of acute ethanol on the levels of NE, DA and its metabolites DOPAC and HVA, as well as on the levels of GABA, in the corpus striatum and hypothalamus were investigated in mice in the first two hours after acute ethanol administration. There was a marked increase in the concentration of DOPAC and HVA in the corpus striatum from 30 to 120 minutes after a dose of 3.5 g/kg of ethanol even though the concentration of DA was only elevated at 60 minutes after ethanol. A dose of 1.75 g/kg of ethanol did not increase DA levels 60 minutes after administration although it did increase the concentration of DOPAC and HVA at this time. In the hypothalamus a dose of 3.5 g/kg of ethanol did not change the concentration of NE or DA but did produce a marked increase in the levels of DOPAC and HVA at 60 and 120 minutes post ethanol. A lower dose of ethanol, 1.75 g/kg, produced the same effect 60 minutes after ethanol. Ethanol caused a dose-dependent accumulation of DOPA in the corpus striatum after inhibition of DOPA-decarboxylase suggesting an increased synthesis of DA. These data suggest that the increased concentrations of DA metabolites after ethanol is secondary to enhanced DA synthesis and turnover. The concentration of NE and GABA in the hypothalamus and the corpus striatum was unchanged at any time period after ethanol.

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Section: Introductionmentioning

confidence: 99%

The effect of acute ethanol on dopamine metabolism and other neurotransmitters in the hypothalamus and the corpus striatum of mice

Dar

Wooles

1984

J. Neural Transmission

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“…We used slice electrophysiology to measure the function of DOR on GABA A R-mediated inhibitory postsynaptic currents (IPSCs) at different time points after EtOH exposure. We also prescreened rats for anxiety (plus maze) and EtOH-induced motor impairment (rotarod), two behaviors that are thought to correlate with potential EtOH consumption (Bacopoulos, Bize, Levine, & Van Orden, 1979; Margolis et al, 2008), in an attempt to determine whether it was possible to predict future EtOH consumption levels and amount of DPDPE-induced inhibition of GABA A R IPSCs in VTA neurons.…”

mentioning

confidence: 99%

Alcohol self-administration, anxiety, and cortisol levels predict changes in delta opioid receptor function in the ventral tegmental area.

Mitchell¹,

Margolis²,

Coker³

2012

Behavioral Neuroscience

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The delta opioid receptor (DOR) agonist DPDPE decreases ethanol (EtOH) consumption when injected into the ventral tegmental area (VTA). We previously showed that DPDPE inhibition of GABAA receptor-mediated inhibitory postsynaptic currents (GABAAR IPSCs) is associated with reduced EtOH consumption. To determine whether self-administration of EtOH is required to change VTA DOR function, we compared the effects of passively administered (gavaged) and self-administered (two-bottle choice) EtOH. Because rats showed variability in DOR regulation of drinking and inhibition of GABAAR IPSCs, we examined whether these changes can be predicted before EtOH exposure by behavioral measures of anxiety or intoxication. Functional DORs were seen with both gavaged and self-administered EtOH, although the magnitude of DPDPE-induced inhibition correlated with behavioral measures only when EtOH was self-administered. Specifically, DPDPE-induced inhibition correlated with predrinking measures of open arm time in the plus maze (n = 19, R = .69, p = .001), with change in maximum fall latency on the rotarod (n = 17, R = .89, p = .000001), and with blood corticosterone (n = 17, R = .66, p = .004) in drinking animals. This DOR-mediated inhibition persisted for at least 14 days after EtOH access was terminated. Together, these findings indicate that anxious animals and those with the greatest EtOH-induced motor impairment have the most robust DPDPE-induced inhibition of GABAAR IPSCs in VTA neurons. These data also extend our understanding of the possible therapeutic value of the DOR for treatment of alcoholism by showing that its relevant synaptic action persists during abstinence.

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“…It modulates ethanol, morphine, and nicotine-associated behaviors [52]–[54]. In rats, apomorphine reverses nicotine-induced changes in the firing rates [55] and population activity [56] of dopamine neurons, and decreases nicotine self-administration [57].…”

Section: Discussionmentioning

confidence: 99%

Larval Zebrafish Model for FDA-Approved Drug Repositioning for Tobacco Dependence Treatment

et al. 2014

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Cigarette smoking remains the most preventable cause of death and excess health care costs in the United States, and is a leading cause of death among alcoholics. Long-term tobacco abstinence rates are low, and pharmacotherapeutic options are limited. Repositioning medications approved by the U.S. Food and Drug Administration (FDA) may efficiently provide clinicians with new treatment options. We developed a drug-repositioning paradigm using larval zebrafish locomotion and established predictive clinical validity using FDA-approved smoking cessation therapeutics. We evaluated 39 physician-vetted medications for nicotine-induced locomotor activation blockade. We further evaluated candidate medications for altered ethanol response, as well as in combination with varenicline for nicotine-response attenuation. Six medications specifically inhibited the nicotine response. Among this set, apomorphine and topiramate blocked both nicotine and ethanol responses. Both positively interact with varenicline in the Bliss Independence test, indicating potential synergistic interactions suggesting these are candidates for translation into Phase II clinical trials for smoking cessation.

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Modification of ethanol intoxication by dopamine agonists and antagonists

Cited by 26 publications

References 19 publications

The effect of acute ethanol on dopamine metabolism and other neurotransmitters in the hypothalamus and the corpus striatum of mice

The effect of acute ethanol on dopamine metabolism and other neurotransmitters in the hypothalamus and the corpus striatum of mice

Alcohol self-administration, anxiety, and cortisol levels predict changes in delta opioid receptor function in the ventral tegmental area.

Larval Zebrafish Model for FDA-Approved Drug Repositioning for Tobacco Dependence Treatment

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