PUBLICATIONS
PUBLICAÇÕES
2025
Background: Alcohol use disorder remains a global issue. Thus, understanding the factors that contribute to alcohol abuse, including how food availability can influence drinking behavior, is critical. Methods: Female and male C57Bl/6 and Swiss mice underwent a two-bottle choice Intermittent Overnight Drinking (IOD) protocol consisting of 12 sessions on alternate nights, three times per week, using lickometer devices. Mice had access to two bottles, containing either water or 10% ethanol, for 16 hours, starting 2 hours before the dark cycle. Animals were initially assigned to two groups: one with access to water, ethanol, and standard rodent chow (FOOD group), and another with access only to water and ethanol (NFOOD group). After six sessions, half of the mice in the second group were reassigned to a new group with delayed access to chow (NFOOD-FOOD group). Results: Food availability led to increased drinking, but the modulation was liquid dependent for each strain. The presence of food primarily increased ethanol intake in C57Bl/6 mice, while it enhanced water intake in Swiss mice. Microstructure analysis revealed that food heightened ethanol licks in C57Bl/6 mice, whereas it elevated water licks in Swiss mice, without altering numbers of bouts. Additionally, overnight analysis showed that C57Bl/6 mice with access to food had a peak in ethanol licks between 20:00 and 22:00, while Swiss mice exhibited an increase in water licks starting at 20:00 to 2:00, highlighting a strain-specific response to the dark cycle. Conclusions: This study provides normative data on the temporal patterns of water and ethanol consumption in C57Bl/6 and Swiss female and male mice, contributing valuable insights to the field of voluntary drinking behaviors in murine models.
2023
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.
2023
Some of these studies indicated energy drinks (ED) can alter the pattern of use and motivation to consume ethanol (EtOH); increase the expression of sensitization to EtOH stimulant effect and the proportion of sensitized mice; decrease the aversiveness of high concentrations of EtOH, among other effects. In addition AmED hastens the loss of righting reflex and its effects on memory are controversial. After acute administration no difference was found in blood ethanol concentration (BEC) of rodents which received EtOH with or without ED, but after 60 days of treatment, AmED group had lower BEC levels than EtOH group. Data on biochemical and neurochemical parameters after AmED are not consistent. Although the AmED group presented higher glucose levels than the EtOH group when drugs were administered by gavage, this was not observed in a self-administration protocol. AmED may induce higher kidney damage, higher levels of plasma urea, uric acid and creatinine when compared to EtOH. Chronic consumption of AmED causes an inflammatory response and oxidative stress, which may induce cell death in the cortex and hypothalamus of adult rats. These controversial results show that AmED diverse effects depend on sex, age and lineage of the animals, duration of the treatment and route of administration. Further research is necessary to evaluate the mechanisms underlying AmED biological effects.
DISTINCT MECHANISMS OF CB1 AND GABAB RECEPTOR PRESYNAPTIC MODULATION OF STRIATAL INDIRECT PATHWAY PROJECTIONS TO MOUSE GLOBUS PALLIDUS
2023
Presynaptic modulation is a fundamental process regulating synaptic transmission. Striatal indirect pathway projections originate from A2A-expressing spiny projection neurons (iSPNs), targeting the globus pallidus external segment (GPe) and control the firing of the tonically active GPe neurons via GABA release. It is unclear if and how the presynaptic G-protein-coupled receptors (GPCRs), GABAB and CB1 receptors modulate iSPN-GPe projections. Here we used an optogenetic platform to study presynaptic Ca2+ and GABAergic transmission at iSPN projections, using a genetic strategy to express the calcium sensor GCaMP6f or the excitatory channelrhodopsin (hChR2) on iSPNs. We found that P/Q-type calcium channels are the primary voltage-gated Ca2+ channel (VGCC) subtype controlling presynaptic calcium and GABA release at iSPN-GPe projections. N-type and L-type VGCCs also contribute to GABA release at iSPN-GPe synapses. GABAB receptor activation resulted in a reversible inhibition of presynaptic Ca2+ transients (PreCaTs) and an inhibition of GABAergic transmission at iSPN-GPe synapses. CB1 receptor activation did not inhibit PreCaTs but inhibited GABAergic transmission at iSPN-GPe projections. CB1 effects on GABAergic transmission persisted in experiments where NaV and KV1 were blocked, indicating a VGCC- and KV1-independent presynaptic mechanism of action of CB1 receptors. Taken together, presynaptic modulation of iSPN-GPe projections by CB1 and GABAB receptors is mediated by distinct mechanisms.
DEVELOPMENT OF EIGHT WIRELESS AUTOMATED CAGES SYSTEM WITH TWO LICK-O-METERS EACH FOR RODENTS.
2022
Drinking behavior has been used in basic research to study metabolism, motivation, decision-making and different aspects of health problems, such as anhedonia and alcohol use disorders. In the majority of studies, liquid intake is measured by weighing the bottles before and after the experiment. This method does not tell much about the drinking microstructure, e.g., licking bouts and periods of preference for each liquid, which could be valuable to understand drinking behavior. To improve the data acquisition of drinking microstructure, companies have developed lick-o-meters devices that acquire timestamps when animals approach or drink from a specific sipper. Nevertheless, commercially available devices have elevated costs. Here, we present a low-cost alternative for a lick-o-meter system that allows wireless data acquisition of licking from eight cages with two sippers each. We run a three-phase validation protocol to ensure 1) proper choice of the sensor to detect licks; 2) adaptation of the device to a wireless transmission and realistic in silico tests; and 3) in vivo tests to correlate the amount of licks measured by the prototype and the bottle weight. The capacitive sensor presented appropriate recall and precision for our device. After adaptation to wireless transmission, the in silico validation demonstrated low reading and transmission errors for the device even when tested in extreme simultaneous licking conditions. Finally, a positive correlation between volume consumption and lick’s count in the in vivo test was observed, showing that the prototype can be used for in vivo studies interested in rodent drinking microstructure.
FOOD COMPOSITION CAN INFLUENCE HOW MUCH ALCOHOL YOUR ANIMAL MODEL DRINKS: A MINI-REVIEW ABOUT THE ROLE OF ISOFLAVONES
2022
Standard laboratory diets 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 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.