Background/Aims: Fluoxetine (FLX) has been widely prescribed for depression during pregnancy and/or lactation. Since serotonin is a neurotrophic factor, the use of FLX by mothers could disrupt brain development resulting in behavioral alterations in their progeny. This study evaluated the effects of developmental FLX exposure on anxiety, depression, aggressivity and pain sensitivity of male and female mice pups. Methods: Swiss dams were treated daily, by gavage, with 7.5 mg/kg of FLX during pregnancy and lactation. Pups were submitted to open-field, forced swimming, elevated plus-maze, intruder-resident and hot plate tests at adolescence and adulthood. Results and Conclusion: In male pups, exposure to FLX decreased ambulation at postnatal day (PND) 40 and tended (p = 0.07) to increase the latency to the first attack in the intruder-resident test at PND 70, suggesting decreased impulsivity. In female pups, FLX exposure increased immobility time in the forced swimming test at both PND 30 and 70, which is interpreted as depressive-like behavior. In conclusion, our results suggest that maternal exposure to FLX during pregnancy and lactation results in enduring behavioral alterations in male and female pups throughout life.

Background Learned associations between environmental stimuli and rewards play a critical role in addiction. Associative learning requires alterations in sparsely distributed populations of strongly activated neurons, or neuronal ensembles. Until recently, assessment of functional alterations underlying learned behavior was restricted to global neuroadaptations in a particular brain area or cell type, rendering it impossible to identify neuronal ensembles critically involved in learned behavior. Methods We used Fos-GFP transgenic mice that contained a transgene with a Fos promoter driving GFP expression to detect neurons that were strongly activated during associative learning, in this case context-independent and context-specific cocaine-induced locomotor sensitization. Whole cell electrophysiological recordings were used to assess synaptic alterations in specifically activated GFP-positive (GFP+) neurons compared to surrounding non-activated GFP-negative (GFP−) neurons 90 min after the sensitized locomotor response. Results Following context-independent cocaine sensitization, cocaine-induced locomotion was equally sensitized by repeated cocaine injections in two different sensitization contexts. Correspondingly, silent synapses in these mice were induced in GFP+ neurons, but not GFP− neurons, following sensitization in both of these contexts. Following context-specific cocaine sensitization, cocaine-induced locomotion was sensitized exclusively in mice trained and tested in the same context (Paired), but not in mice that were trained in one context and then tested in a different context (Unpaired). Silent synapses increased in GFP+ neurons, but not in GFP− neurons from Paired mice but not from Unpaired mice. Conclusions Our results indicate that silent synapses are formed only in neuronal ensembles of the nucleus accumbens shell that are related to associative learning.

There were no differences between male and female rats in context-induced reinstatement of alcohol-seeking behavior. Re-exposure to Context A, but not Context B, reinstated alcohol-seeking behavior and increased expression of the neural activity marker Fos in the OFC. Reversible inactivation of the OFC with muscimol and baclofen attenuated context-induced reinstatement. Our data indicated that the OFC mediates context-induced reinstatement of alcohol-seeking behavior.

The capacity of rodents to recognize and respond to emotional signs from a conspecific is a valuable adaptive behavior, which provides essential skills for species survival. However, repeated exposure to aversive situations may elicit maladaptive behavioral responses in subjects that experience noxious episodes and their colony members. Previous findings by our group demonstrated that living with a subject in neuropathic pain induces anxiogenic-like behaviors and hypernociception in mice. Whereas chronic pain may be considered a stressful stimulus, we extended our findings on stress-induced emotional transfer. For this purpose, we investigated whether cohabitation with a partner subjected to chronic restraint stress was able to promote alterations in anxiety-like behaviors, pain sensibility and defensive responses. Male Swiss mice were housed in pairs for 14days and then separated into control, stress, and cagemate groups. The stress group was subjected to 14days of restraint stress (1h/day) in the presence of the cagemates, while the pair-housed control group was left undisturbed. A day after last stress session control, stress, and cagemate groups were evaluated using elevated plus maze test, writhing test, and rat exposure test. Results demonstrated that chronic stress attenuated weight gain in the stress group. Moreover, cohabitation with mice subjected to chronic restraint stress induced anxiogenic-like behaviors, pain hypernociception, and alterations in defensive responses in both cagemate and stress groups. These preliminary findings suggest that chronic exposure to aversive stimulus may induce behavioral alterations even in observers.

Background: Alcohol abuse is a health concern worldwide. Studies have associated alcohol abuse with cardiovascular impairments. In this study, we investigated differences in the effects of chronic alcohol vapor exposure on cardiovascular function between male and female rats by using the alcohol vapor chamber method to induce alcohol addiction-like behaviors in rats.Methods: We exposed male and female Long-Evans rats to alcohol vapor for 14 hours, followed by ethanol withdrawal for 10 hours, for 30 consecutive days or room air (control groups). The animals underwent preparation for the surgical implantation of cannulas into femoral vessels, for allowing the assessment of the basal arterial pressure and heart rate values, baroreflex function, and autonomic activity.Results: Female control rats showed higher basal heart rate compared to male control rats. Chronic alcohol vapor inhalation reduced basal heart rate in females, but not in males; this effect was followed by an increase in the parasympathetic tone of the heart. Further, female rats subjected to alcohol vapor showed an increase in the baroreflex activity.Conclusions: These findings suggest that females are more sensitive to chronic alcohol vapor exposure than males because they had a reduction in basal heart rate and changes in the baroreflex activity.

Evidence indicates that drug relapse in humans is often provoked by exposure to the self-administered drug-associated context. An animal model called “ABA renewal procedure” has been used to study the context-induced relapse to drug seeking. Here, we reported a new and feasible training procedure for the ABA renewal method to explore the role of the prelimbic cortex in context-induced relapse to ethanol seeking. By using a saccharin fading technique, we trained rats to self-administer ethanol (10%). The drug delivery was paired with a discrete tone-light cue. Lever pressing was subsequently extinguished in a non-drug-associated context in the presence of the discrete cue. Rats were subsequently tested for reinstatement in contexts A or B, under extinction conditions. Ethanol-associated context induced the reinstatement of ethanol seeking and increased the expression of Fos in the prelimbic cortex. The rate of neural activation in the prelimbic cortex was 3.4% in the extinction context B and 7.7% in the drug-associated context A, as evidenced by double-labeling of Fos and the neuron-specific protein NeuN. The reversible inactivation of the neural activity in the prelimbic cortex with gamma-Aminobutyric acid (GABA) receptor agonists (muscimol + baclofen) attenuated the context-induced reinstatement of ethanol self-administration. These results demonstrated that the neuronal activation of the prelimbic cortex is involved in the context-induced reinstatement of ethanol seeking.

The affective component of pain may be shared among conspecifics through emotional contagion, a form of empathic expression. In this sense, reverberation of negative emotions could generate distress behavioral responses, such as pathological anxiety. Evidences reported that amygdala and its benzodiazepine receptors are involved in perception of pain in others. However, relatively little is known about the neural processes underlying emotional contagion induced by pain observation. In the present study, we investigated the effects of midazolam, an allosteric GABAergic receptor agonist, in anxiety-like behaviors induced by cohabitation with cagemate submitted to sciatic nerve constriction. For this purpose, we administrated systemic (0.5, 1.0 and 2.0 mg/kg) and intra-amygdala midazolam injections (3.0 and 30.0 nmol) in observer cagemates before elevated plus-maze (EPM) evaluation. We found that mice subjected to nerve constriction and their observer cagemates increased anxiety-like behavior in the EPM. Further, systemically (1.0 and 2.0 mg/kg) and intra-amygdala administration of midazolam (3.0 and 30 nmol) reverse this anxiogenic effect. Collectively, these results suggest that social interaction with a cagemate under chronic pain produces anxiety-like responses that could be blocked through midazolam application.

While clinical and pre-clinical evidence suggests that adolescence is a risk period for the development of addiction, the underlying neural mechanisms are largely unknown. Stress during adolescence has a huge influence on drug addiction. However, little is known about the mechanisms related to the interaction among stress, adolescence and addiction. Studies point to ΔFosB as a possible target for this phenomenon. In the present study, adolescent and adult rats (postnatal day 28 and 60, respectively) were restrained for 2 h once a day for 7 days. Three days after their last exposure to stress, the animals were challenged with saline or amphetamine (1.0 mg/kg i.p.) and amphetamine-induced locomotion was recorded. Immediately after the behavioral tests, rats were decapitated and the nucleus accumbens was dissected to measure ΔFosB protein levels. We found that repeated restraint stress increased amphetamine-induced locomotion in both the adult and adolescent rats. Furthermore, in adult rats, stress-induced locomotor sensitization was associated with increased expression of ΔFosB in the nucleus accumbens. Our data suggest that ΔFosB may be involved in some of the neuronal plasticity changes associated with stress induced-cross sensitization with amphetamine in adult rats.