Food composition can influence how much alcohol your animal model drinks: A mini-review about the role of isoflavones.

Standard laboratory diets used have similar concentrations of proteins, carbohydrates and fat, but the concentration of some micronutrients can vary considerably. For example, the concentration of isoflavones can vary between 20 mg and 600 mg per gram of diet. Exposure to different concentrations of isoflavones interacts with alcohol (EtOH) intake, thereby influencing the results of alcohol research. In this mini-review, we describe correlations between isoflavone concentrations and alcohol intake based on data from previously published work. Although the administration of low doses of isoflavones can decrease alcohol intake in rats, there is a positive correlation between the isoflavone content in diets and alcohol intake in mice. This interaction seems to depend on the dose, route of administration, and time of exposure to isoflavones and may be related to specific neurobiological mechanisms. The literature also indicates that isoflavones can interact with some of alcohol's molecular targets and with neural pathways crucial to the alcohol reward process. Given these findings, more attention should be given to the different types of laboratory diets used in alcohol studies to allow better comparison and replication of animal research.

Administration of the 5-HT2C receptor antagonist SB-242084 into the nucleus accumbens blocks the expression of ethanol-induced behavioral sensitization in Albino Swiss mice.

Behavioral sensitization to the stimulating effect of ethanol (EtOH) or other drugs, which can be observed in mice as an increase in locomotor activity after repeated administration, has been associated with neuroadaptations within the dopaminergic mesolimbic pathway. In the nucleus accumbens (NAc), an afferent region of the mesolimbic pathway, dopamine (DA) release can be modulated by serotonergic 2C receptors (5-HT2CR). The aim of the present study was to evaluate the function of 5-HT2CR in the expression of EtOH-induced behavioral sensitization in Albino Swiss mice with various levels of sensitization to EtOH. In the four experiments that we performed, the mice were given saline or 2.2 g/kg EtOH daily for 21 days. Based on their locomotion on day 21, the EtOH-pretreated mice were assigned to one of two groups, highly sensitized or weakly sensitized to the stimulating effect of EtOH. In each experiment, 2 weeks after the 21-day treatment (withdrawal period), the mice were submitted to four pharmacological challenges of two drug treatments each. The mice in experiments 1 and 2 received two i.p. injections, whereas the mice in experiments 3 and 4 received an intra-NAc administration followed by an i.p. injection. The challenges were: saline+saline; saline+EtOH; SB-242084 (a 5-HT2CR antagonist; 0.5, 1.0 or 2.0 mg/kg i.p. or 1.0 or 2.0 µg/side intra-NAc)+EtOH; and SB-242084 (0.5, 1.0 or 2.0 mg/kg i.p. or 1.0 or 2.0 µg/side intra-NAc)+saline. At all tested doses, i.p. administration of SB-242084 did not affect the stimulating effect of EtOH in the highly sensitized mice. However, when delivered by intra-NAc administration, SB-242084 reduced (at 1.0 µg/side) or completely blocked (at 2.0 µg/side) the expression of EtOH-induced behavioral sensitization in the highly sensitized mice. These findings suggest that the expression of behavioral sensitization to the stimulating effect of EtOH depends on accumbal 5-HT2CR activity.

Morphine attenuates the expression of sensitization to ethanol, but opioid antagonists do not.

Behavioral sensitization to ethanol is characterized by an increased locomotor activity after repeated exposure. A great variability exists among species and strains in the development of sensitization. There is a growing amount of evidence to indicate that the opioid system is involved in alcoholism; it is possible, therefore, that this system also modulates the sensitization to ethanol. In this study we evaluated the role of the opioid system in determining the variability of the sensitized response to ethanol. Mice received repeated administrations of ethanol (2.2 g/kg) or saline every other day for 10 days. According to their locomotor response on the last day of treatment, ethanol-treated animals were classified into two groups: sensitized or non-sensitized mice. After the treatment, mice were submitted to four challenges 48 h apart. In experiments 1 and 2, mice were challenged, respectively, with i.p. administration of opioid antagonists (naloxone or naltrexone) or an opioid agonist (morphine), followed immediately by 2.2 g/kg ethanol. In experiment 3, animals received morphine by i.c.v., followed by 2.2 g/kg of ethanol (i.p.). Pretreatment with opioid antagonists (naloxone or naltrexone) did not block the expression of ethanol sensitization; however pretreatment with morphine attenuated the increased locomotor activity after ethanol administration in sensitized mice. In experiment 4, after the ethanol or saline treatment, mice brains were processed and brain mu opioid binding was assessed by autoradiography using [3H]D-Ala2,N-mePhe4, Gly-ol5-enkephalin ([3H]DAMGO). No differences were seen between any of the groups of mice, so the agonist effect is not likely to be mediated by differences in binding to mu opioid receptors.