Arthur H. Briggs

Enkephalinase inhibition: regulation of ethanol intake in genetically predisposed mice.

This is the first report of alteration in alcohol intake in mice with a genetic predisposition to alcohol preference and known to have innate brain enkephalin deficiencies. We have been able to significantly attenuate both volitional and forced ethanol intake respectively by acute and chronic treatment with hydrocinnamic acid and D-phenylalanine, known carboxypeptidase (enkephalinase) inhibitors. Since these agents, through their enkephalinase inhibitory activity, raise brain enkephalin levels, we propose that excessive alcohol intake can be regulated by alteration of endogenous brain opioid peptides.

Ethanol ingestive behavior as a function of central neurotransmission.

Uncontrollable alcohol ingestive behavior has been linked to deficits of central neurotransmission. The pineal gland plays an important role in modulating ethanol intake in numerous animal species. The opioidergic (i.e. β-endorphin, enkephalin, and dynorphin) system is involved in both the actions of alcohol and opiates, as well as craving and/or genetic predisposition towards abuse of these two agents. Furthermore, there is significant evidence to link ingestive behaviors with the ventral tegmental accumbens-hypothalamic axis, whereby the biogenic amines dopamine and serotonin are reciprocally involved. Evidence is presented which implicates the striatum and the hypothalamus as possible specific loci for regional differences between alcohol-preferring and alcohol-nonpreferring mice. We believe that photoperiod-induced alcohol ingestive behavior may involve alterations in both pineal and hypothalamic opioid peptides.

Whole brain methionine-enkephalin of ethanol-avoiding and ethanol-preferring C57BL mice

These experiments systematically investigated ethanol preference in both the C57Bl/6N and C57Bl/6J mice utilizing three-choice 2-bottle preference test. In addition, these sublines were evaluated for whole brain methionineenkephalin levels, which were significantly lower in C57Bl/6J mice (alcohol preferring) compared to C57Bl/6N mice (alcohol non-preferring). This finding supports the involvement of the peptidyl opiates in ethanol seeking behavior.

Regional brain [Met]-enkephalin in alcohol-preferring and non-alcohol-preferring inbred strains of mice

Scrutiny of the data from these studies reveals that the C58/J alcohol-preferring mice have significantly lower baseline methionine-enkephalin levels in both the corpus striatum and hypothalamus compared to C3H/CHRGL/2 non-alcohol-preferring mice. In other brain regions in these two strains, specifically, pituitary, amygdala, midbrain, and hippocampus, analysis of methionine-enkephalin levels did not show any significant differences. This suggests that the hypothalamus may indeed be a specific locus involved in the regulation of alcohol intake, via the molecular interaction between neuroamines, opioid peptides, as they are influenced by genetics and environment.

Ethanol intoxication as function of genotype dependent responses in three inbred mice strains

Three strains of mice, ICR Swiss, DBA/2J and C57Bl/6J were compared for initial sensitivity, recovery from intoxication, and acute tolerance development to ethanol. The The C57Bl/6J mice were found to be less sensitive and to recover more rapidly from the effects of the same dose of ethanol than the other two strains treated. None of the strains tested demonstrated acute tolerance to ethanol when given the same dose 3 hours later.

Single-dose fasting bioequivalence assessment of erythromycin stearate tablets in man

The bioequivalence of film-coated erythromycin stearate tablets produced by five different manufacturers was evaluated in a balanced incomplete block design involving the five formulations given to 30 fasted subjects over a 3-week study period. Serum levels of erythromycin activity were determined microbiologically. Statistical analysis of variance was performed on the observed bioavailability parameters: maximum serum concentration Cmax, time to maximum serum concentration (tmax), and area under the serum concentrationtime curve (AUC). There was no statistical difference between formulations for the tmax parameter. Formulation differences were found, however, based on the analysis of variance of the Cmax and AUC parameters. Two products, although not significantly different from one another, showed significantly greater Cmax and AUC values than the other three products.

A rapid method to evaluate acute ethanol intoxication in mice

A simple technique for the evaluation of ethanol intoxication based on the ability of mice to remain on a bar suspended above an electrified grid is reported. The characteristics that make this model useful to measure ethanol induced intoxication include: (a) low variability; (b) high sensitivity; (c) rapidity; (d) requires no previous training of animals to be tested; (e) objective scoring which can be quantified; and (f) dose-dependent correlation between brain and blood ethanol levels and bar holding response.

Supersensitivity to norepinephrine induced by prenatal exposure to ethanol

Pregnant random bred mice were treated with ethanol (ETOH) (0.33 g/kg) for 1 or 2 days prior to parturition. When compared to saline controls, ETOH-treated adult males had vasa deferentia that were supersensitive to norepinephrine (NE). Tissues from mice prenatally treated for 1 day with ETOH showed a decreased response to electrical stimulation whereas vas deferens obtained from 2-day-treated ethanol showed no significant difference in the response compared to that of controls. These findings indicate that prenatal exposure to ETOH can influence the subsequent sensitivity of the vas deferens to adrenergic stimulation. These changes appear to reflect effects of ETOH during critical periods.