Memory and anxiety-like behavior of rats in the plus-maze discriminative avoidance task: Role of serotonergic transmission in the basolateral amygdala.

Optimal levels of anxiety are critical to memory consolidation, but maladaptive anxiety can disrupt memory acquisition. Serotonergic activity within the amygdala influences both anxiety-like behavior and aversive memory consolidation. To evaluate the effects of serotoninergic manipulations within the basolateral amygdala (BLA) on anxiety-like behavior and aversive memory in rats tested in the plus-maze discriminative avoidance task (PMDAT). The PMDAT investigates aversive memory and anxiety-like behavior simultaneously in rodents. Three-month-old male Wistar rats received bilateral infusions (1 µL per side) of saline, 8-OH-DPAT (5-HT1 agonist; 10 nmol), WAY100135 (5-HT1 antagonist; 0.9 nmol), ketanserine (5-HT 2 antagonist; 10 nmol), or fluoxetine (serotonin reuptake inhibitor; 1.6 nmol) into the BLA and were submitted to PMDAT training session 15 min later. In the test, 24 hr later, animals were re-exposed to the apparatus without the infusion of drugs, and aversive memory was evaluated. (a) 8-OH-DPAT did not affect memory or anxiety, but impaired avoidance behavior toward the aversive arm during training; (b) fluoxetine, WAY100135 and ketanserin impaired memory formation; (c) ketanserin decreased anxiety-like behavior; and (d) none of the treatments induced motor changes. The results showed that an increase in serotonin (5-HT) availability or the blockade of 5HT1A and 5HT2A BLA receptors impaired aversive memory formation. However, only 5HT2A receptor antagonism induced anxiolytic effects. Thus, both memory and anxiety-like behavior can be modified by changes in serotonergic transmission in the basolateral amygdala, but the effects on both phenomena seem to be mediated by different mechanisms related to serotonergic transmission. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Neuroinflammation in early, late and recovery stages in a progressive parkinsonism model in rats.

Parkinson's disease (PD) is characterized by motor and non-motor signs, which are accompanied by progressive degeneration of dopaminergic neurons in the substantia nigra. Although the exact causes are unknown, evidence links this neuronal loss with neuroinflammation and oxidative stress. Repeated treatment with a low dose of reserpine-inhibitor of VMAT2-has been proposed as a progressive pharmacological model of PD. The aim of this study was to investigate whether this model replicates the neuroinflammation characteristic of this disease. Six-month-old Wistar rats received repeated subcutaneous injections of reserpine (0.1 mg/kg) or vehicle on alternate days. Animals were euthanized after 5, 10, or 15 injections, or 20 days after the 15th injection. Catalepsy tests (motor assessment) were conducted across treatment. Brains were collected at the end of each treatment period for immunohistochemical and RT-PCR analyzes. Reserpine induced a significant progressive increase in catalepsy duration. We also found decreased immunostaining for tyrosine hydroxylase (TH) in the substantia nigra pars compacta (SNpc) and increased GFAP + cells in the SNpc and dorsal striatum after 10 and 15 reserpine injections. Phenotyping microglial M1 and M2 markers showed increased number of CD11b + cells and percentage of CD11b + /iNOS + cells in reserpine-treated animals after 15 injections, which is compatible with tissue damage and production of cytotoxic factors. In addition, increased CD11b + /ArgI + cells were found 20 days after the last reserpine injection, together with an increment in IL-10 gene expression in the dorsal striatum, which is indicative of tissue repair or regeneration. Reserpine also induced increases in striatal interleukin TNF-alpha mRNA levels in early stages. In view of these results, we conclude that reserpine-induced progressive parkinsonism model leads to neuroinflammation in regions involved in the pathophysiology of PD, which is reversed 20 days after the last injection. These findings reveal that withdrawal period, together with the shift of microglial phenotypes from the pro-inflammatory to the anti-inflammatory stage, may be important for the study of the mechanisms involved in reversing this condition, with potential clinical applicability.

Sex differences in the acute ethanol effects on object recognition memory: influence of estrous cycle.

Effects of acute ethanol (EtOH) on memory depend on several factors, including type of behavioral task. Sex differences in EtOH effects have been reported in humans and animals, and recognition memory can be influenced by circulating sex hormones. The aim of this study was to investigate the influence of sex and estrous cycle in the acute effects of EtOH on novel object recognition memory in rats. Male and female Wistar rats were part of one of the groups: control, 0.6-g/kg EtOH and 1.8-g/kg EtOH (administered intraperitoneally before the training session). The estrous cycle was evaluated by vaginal smear. The task was conducted in an open field arena. During training, animals were exposed to two identical objects, and test sessions were performed 1 h (short-term) and 24 h (long-term) later. One of the objects was changed in each test. Increased novel object exploration was shown by male and female controls in the short- and long-term tests, respectively. In the short-term test, females did not show preference for the novel object, and EtOH 1.8 g/kg impaired performance in males. In the long-term test, both sexes showed object discrimination, and 1.8-g/kg EtOH reduced preference for the new object in male rats. The phase of the cycle, the performance on proestrus was worse compared with other phases, and EtOH failed to impair performance mainly on estrous. In conclusion, while male rats displayed ethanol-induced recognition memory deficit, female rats were unaffected by EtOH impairing effects. In addition, the performance of female rats was influenced by the estrous cycle phases.

Female Rats Are Resistant to Cognitive, Motor and Dopaminergic Deficits in the Reserpine-Induced Progressive Model of Parkinson's Disease.

Parkinson's disease (PD) is the second most common neurodegenerative disease. The main symptoms are motor signs such as resting tremor and difficulty in initializing movements. Non-motor alterations, such as cognitive deficits, can precede the motor symptoms. PD is more frequent in men than women. The mechanisms related to this difference are not completely understood. There is evidence that females present distinct characteristics in dopaminergic function compared to males. While the severity of motor impairments is often compared between sexes, little is known about sex differences in the prodromal stage. Most animal models of PD present acute severe motor impairment, which precludes the study of non-motor symptoms. Our research group have proposed an adaptation of the classic reserpine protocol, using low doses in a chronic treatment. This method allows the observation of progressive motor impairment as well as premotor deficits. Here we investigate possible behavioral and neuronal sex differences in the effects of the repeated treatment with a low dose of reserpine in rats. Male and female Wistar rats received 10-15 injections of reserpine (0.1 mg/kg) or vehicle, on alternate days. We followed-up the estrous cycle phases and conducted motor and cognitive assessments (catalepsy, open field, oral movements and object recognition tests). The euthanasia occurred 48 h after the 10th or 15th injections, with the collection of blood for the quantification of sex hormones and brains for tyrosine hydroxylase (TH) immunohistochemistry in the substantia nigra pars compact (SNpc). Reserpine induced progressive catalepsy, involuntary oral movements and cognitive deficits in male rats. The behavioral effects of reserpine were attenuated (motor) or absent (cognitive) in females. Reserpine decreased TH immunoreactivity in males, but not in females. Estrogen levels in females negatively correlated with catalepsy duration. Our findings show that females present a delay and/or a prevention in the reserpine-induced motor alterations in the progressive PD model, compatible with the lower prevalence of this disease in women. Further, females were protected from the deficit in object recognition at the prodromal stage. The absence of reserpine-induce decrease in TH immunoreactivity suggests that differences in dopaminergic function/plasticity are related to this protection in female sex.

Impaired discriminative avoidance and increased plasma corticosterone levels induced by vaginal lavage procedure in rats.

Historically, females have been neglected in behavioral neuroscience research due to the alleged increased variability caused by hormonal fluctuations. More recently, there has been a tendency to include female subjects in the studies, in a majority of those cases with the condition that the hormonal variation is controlled. In rodent studies, the vaginal lavage procedure is a common method of collecting smears and determining the estrous cycle phase. However, little is known regarding the consequences of the procedure, although stress is often mentioned as a concern. Within the neuroscience field, spatial memory has been a relevant subject in terms of sex differences. The plus-maze discriminative avoidance task (PMDAT) allows for the concomitant evaluation of spatial memory, anxiety-like behavior, and locomotion, as well as possible interactions between these behaviors. The aim of the present study was to investigate the effects of the vaginal lavage procedure (VLP) on the performance of female rats in the  PMDAT. We submitted adult female Wistar rats to VLP for 14 straight days and then to training and test sessions in the PMDAT. Additionally, another set of animals was submitted to the VLP procedure for determination of plasma corticosterone levels. Rats submitted to the vaginal lavage procedure did not discriminate the enclosed arms of the PMDAT apparatus, indicating impaired performance, but no anxiety-like alterations were found. VLP also resulted in a higher corticosterone level, suggesting it is a stressful manipulation. As such, the use of this method to control for hormonal variation should be restricted in behavioral studies.