Expression of behavioral sensitization to ethanol is increased by energy drink administration

Alcohol abuse and dependence are important medical, social and economical problems, affecting millions of people. A relatively recent habit among young people is mixing alcohol with energy drinks (ED), in spite of the risks involved may be higher than those associated with alcohol consumption alone. the mixture of alcohol and energy drinks, both with stimulant properties, may alter the perception of intoxication and could lead individuals to believe they are less drunk and can drink more or for longer periods of time. in animals, the repeated administration of ethanol can lead to a progressive increase of the locomotor stimulant effect, known as behavioral sensitization, a drug-dependent behavioral plasticity associated with vulnerability to addiction. As well as for addiction, there are clear individual differences in the level of sensitization to ethanol among species and even among individuals from the same strain. the present study assessed how ED affects the expression of ethanol sensitization. Female mice chronically treated with ethanol (2.4 g/kg) were classified as low-sensitized or high-sensitized. Two days later, different groups of mice were submitted to saline + water, ethanol + water or ethanol + ED systemic challenges. As expected, only the high-sensitized group expressed clear sensitization after ethanol administration. However, the administration of ethanol + ED triggered the sensitization expression in the low-sensitized group. These data indicate that the combined use of ED and ethanol can potentiate the stimulant and, consequently, the reward effects of ethanol in previously treated mice. If a similar process occurs in human beings, the use of ED can increase the risk of developing alcohol abuse or dependence. (C) 2013 Elsevier Inc. All rights reserved.Associacao Fundo de Incentivo a Pesquisa (AFIP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Universidade Federal de São Paulo UNIFESP, Dept Ps Biol, Esco Paulista Med, BR-04023062 São Paulo, BrazilUniversidade Federal de São Paulo UNIFESP, Dept Ps Biol, Esco Paulista Med, BR-04023062 São Paulo, BrazilFAPESP: FAPESP 02/04191-0Web of Scienc

Distinct behavioral phenotypes in ethanol-induced place preference are associated with different extinction and reinstatement but not behavioral sensitization responses

Conditioned place preference (CPP) is a model to study the role of drug conditioning properties. in outbred strains, individual variability may affect some behavioral measures. However, there are few studies focusing on understanding how different phenotypes of ethanol conditioned behavior may influence its extinction, reinstatement, and behavioral adaptation measures. We used male Swiss Webster mice to study different phenotypes related to ethanol conditioning strength, reinstatement and behavioral sensitization. Mice went through a CPP procedure with ethanol (2.2 g/kg, i.p.). After that, one group of mice was submitted to repeated extinction sessions, while another group remained in their home cages without any drug treatment. Mice went through environmental and ethanol priming (1.0 g/kg, i.p.) reinstatement tests. Ethanol priming test reinstated the conditioned behavior only in the animals kept in the home-cage during the abstinence period. Besides, the ethanol conditioned behavior strength was positively correlated with the time required to be extinguished. in the second set of experiments, some mice went through a CPP protocol followed by behavioral sensitization (five i.p. administrations of ethanol 2.2 g/kg or saline per week, for 3 weeks) and another group of mice went through sensitization followed by CPR No positive correlation was observed between ethanol CPP strength and the intensity of behavioral sensitization. Considering that different phenotypes observed in CPP strength predicted the variability in other CPP measures, we developed a statistics-based method to classify mice according to CPP strength to be used in the evaluation of ethanol conditioning properties.Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)AFIPFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Universidade Federal de São Paulo, Dept Psicobiol, Unidade Dependencia Drogas, São Paulo, BrazilNIAAA, Lab Integrat Neurosci, NIH, Rockville, MD 20852 USAUniversidade Federal de São Paulo, Dept Psicobiol, Unidade Dependencia Drogas, São Paulo, BrazilFAPESP: 2011/15258-8Web of Scienc

Where do you measure the Bregma for rodent stereotaxic surgery?

The advent of the stereotaxic apparatus developed by Clarke and Horsley revolutionized neuroscience research, enabling precise 3D navigation along the skull mediolateral, anteroposterior, and dorsoventral axes. In rodents, the Bregma is widely used as the origin reference point for the stereotaxic coordinates, but the specific procedure for its measurement varies among different laboratories. Notably, the renowned brain atlas developed by Paxinos and Franklin lacks explicit instructions on the Bregma determination. Recent studies have found discrepancies in skull and brain landmark measurements. This review describes the commonly used brain atlases and highlights the limitations in accurately measuring the stereotaxic coordinates. In addition, we propose alternative and more reliable approaches to measure the Bregma. It is imperative to address the misconceptions about the accuracy of stereotaxic surgeries, as it can significantly impact a substantial portion of neuroscience research

Experiment 2.

<p>(A) Ethanol consumption for 2 h/day during 15 days of acquisition phase. (B-D) Elevated plus maze test: (B) percent time on open arms, (C) number of open arm entries, and (D) total number of arm entries. (E) Ethanol intake during 2 h access to two-bottle choice once per week. Ethanol intake calculations followed the same criteria as described for the first experiment. (F) Ethanol intake (g/kg) during 24 h of access to two-bottle choice on weeks 3 and 4. (G) Water intake during 2 h access to two-bottle choice. Water intake calculations followed the same criteria as described for the first experiment. (H) Water intake (ml) during 24h. Gray bars represent the measures of intake after exposure to the restraint stress procedure. The data are expressed as mean ± SEM. *<i>p</i> < 0.05, compared with day 3 in A, compared with the other re-exposure weeks in E, and compared with the EE group on the previous week without stress in F; ⁺<i>p</i> < 0.05, compared with SC group; ^#<i>p</i> < 0.05, compared with weeks 2 and 3.</p

Environmental Enrichment Blunts Ethanol Consumption after Restraint Stress in C57BL/6 Mice

<div><p>Elevated alcohol intake after abstinence is a key feature of the addiction process. Some studies have shown that environmental enrichment (EE) affects ethanol intake and other reinforcing effects. However, different EE protocols may vary in their ability to influence alcohol consumption and stress-induced intake. The present study evaluated whether short (3 h) or continuous (24 h) EE protocols affect ethanol consumption after periods of withdrawal. Mice were challenged with stressful stimuli (24 h isolation and restraint stress) to evaluate the effects of stress on drinking. Male C57BL/6 mice were subjected to a two-bottle choice drinking-in-the-dark paradigm for 15 days (20% ethanol and water, 2 h/day, acquisition phase). Control mice were housed under standard conditions (SC). In the first experiment, one group of mice was housed under EE conditions 24 h/day (EE24h). In the second experiment, the exposure to EE was reduced to 3 h/day (EE3h). After the acquisition phase, the animals were deprived of ethanol for 6 days, followed by 2 h ethanol access once a week. Animals were tested in the elevated plus maze (EPM) during ethanol withdrawal. During the last 2 weeks, the mice were exposed to 24 h ethanol access. A 1-h restraint stress test was performed immediately before the last ethanol exposure. EE24h but not EE3h increased anxiety-like behavior during withdrawal compared to controls. Neither EE24h nor EE3h affected ethanol consumption during the 2 h weekly exposure periods. However, EE24h and EE3h mice that were exposed to acute restraint stress consumed less ethanol than controls during a 24 h ethanol access. These results showed that EE reduces alcohol intake after an acute restraint stress.</p></div

Experiment 1.

<p>(A) Ethanol consumption for 2 h/day during 15 days of acquisition phase. (B) Blood ethanol concentration (mg/ml) plotted against ethanol consumed (g/kg) during 2 h of ethanol access. Positive correlation was found between the amount of ethanol consumed and BECs (<i>r</i>^<i>2</i> = 0.41, <i>p</i> < 0.05). (C-E) Elevated plus maze test: (C) percent time on open arms, (D) number of open arm entries, and (E) total number of arm entries. (F) Ethanol intake during 2 h access to two-bottle choice once a week. Ethanol intake was converted to percent of basal ethanol consumption. Basal ethanol consumption was calculated by averaging the absolute consumption of the last 5 days of acquisition phase, and converted as 100% (week 0). (G) Ethanol intake (g/kg) during 24 h of access to two-bottle choice on weeks 5 and 6. (H) Water intake (ml) during 2 h access to two-bottle choice. Water intake was converted to percent of basal water consumption. Basal water consumption was calculated by averaging the absolute consumption of the last 5 days of acquisition phase, and converted as 100% (week 0). (I) Water intake (ml) during 24 h. Gray bars represent the measures of intake after exposure to the restraint stress procedure. The data are expressed as mean ± SEM, except in B. *<i>p</i> < 0.05, compared with days 1, 2, and 3 in A, compared with prior re-exposure weeks in F, H, and I, and compared with the EE group on the previous week without stress in G; ⁺<i>p</i> < 0.05, compared with SC group.</p