Chronic unpredictable restraint stress increases hippocampal pro-inflammatory cytokines and decreases motivated behavior in rats.

Most chronic stress protocols are too laborious or do not abide by the two main characteristics of the stress concept: uncontrollability and unpredictability. The goal of this study was to establish a simple and reliable model of chronic stress, while maintaining the main features of the concept. Animals were exposed to chronic movement restraint with variable duration (2, 4 or 6 h, in an unpredictable schedule) for 3 weeks and assessed in several physiological and behavioral readouts known to reflect chronic stress states. Body weight, levels of plasma corticosterone, hippocampal pro-and anti-inflammatory cytokines, anxiety-like (novelty suppressed feeding and elevated plus maze) and motivated behaviors (sucrose negative contrast test and forced swim test) were evaluated three days after the end of the chronic protocol. Stressed animals had a lower body weight gain, higher levels of cytokines in the hippocampus, reduced suppression of a low concentration sucrose solution and increased immobility in the forced swim test. Based on these data, we suggest that chronic movement restraint with variable duration may be a suitable and simple protocol for the study of changes induced by chronic stress and for the testing of possible treatments relevant to psychiatry.

Effects of GABAa receptor antagonists on motor behavior in pharmacological Parkinson's disease model in mice.

The aim of this study was to evaluate the effects of two gamma-amino butyric acid (GABA)a receptor antagonists on motor behavioral tasks in a pharmacological model of Parkinson disease (PD) in rodents. Ninety-six Swiss mice received intraperitoneal injection of Haloperidol (1 mg/kg) to block dopaminergic receptors. GABAa receptors antagonists Bicuculline (1 and 5 mg/kg) and Flumazenil (3 and 6 mg/kg) were used for the assessment of the interaction among these neurotransmitters, in this PD model. The motor behavior of the animals was evaluated in the catalepsy test (30, 60, and 90 min after drugs application), through open field test (after 60 min) and trough functional gait assessment (after 60 min). Both Bicuculline and Flumazenil were able to partially reverse catalepsy induced by Haloperidol. In the open field test, Haloperidol reduced the number of horizontal and vertical exploration of the animals, which was not reversed trough application of GABAa antagonists. Furthermore, the functional gait assessment was not sensitive enough to detect motor changes in this animal model of PD. There is an interaction between dopamine and GABA in the basal ganglia and the blocking GABAa receptors may have therapeutic potential in the treatment of PD.