Restraint-induced hypoactivity in an elevated plus-maze

Rodents submitted to restraint stress show decreased activity in an elevated plus-maze (EPM) 24 h later. The objective of the present study was to determine if a certain amount of time is needed after stress for the development of these changes. We also wanted to verify if behavioral tolerance of repeated daily restraint would be detectable in this model. Male Wistar rats were restrained for 2 h and tested in the EPM 1, 2, 24 or 48 h later. Another group of animals was immobilized daily for 2 h for 7 days, being tested in the EPM 24 h after the last restraint period. Restraint induced a significant decrease in the percent of entries and time spent in the open arms, as well as a decrease in the number of enclosed arm entries. The significant effect in the number of entries and the percentage of time spent in the open arms disappeared when the data were submitted to analysis of covariance using the number of enclosed arm entries as a covariate. This suggests that the restraint-induced hypoactivity influences the measures of open arm exploration. The modifications of restraint-induced hypoactivity are evident 24 or 48 h, but not 1 or 2 h, after stress. In addition, rats stressed daily for seven days became tolerant to this effect

Pinealectomy attenuates the effect of restraint on plus maze exploration in rats

To investigate a possible stress modulation role of the pineal gland, male Wistar albino rats (200-250 g) were submitted to pinealectomy and divided into four groups one week after surgery: i) sham-operated unrestrained animals (N = 14); ii) pinealectomized unrestrained animals (N = 22); iii) sham-operated animals submitted to 2 h of restraint (N = 52); iv) pinealectomized animals submitted to 2 h of restraint (N = 56). Twenty-four hours later the animals were tested in the elevated plus maze for 5 min. Pinealectomized rats submitted to restraint explored the open arms of the maze to a greater extent than sham-operated restrained rats (mean percent of open arm entries = 26.4 ñ 2.3 vs 18.0 ñ 2.1, mean percent of time spent in the open arms = 11.8 ñ 2.1 vs 6.8 ñ 1.2). Pinealectomized animals not submitted to restraint showed no difference in maze exploration when compared to sham-operated rats (mean percent of open arm entries = 29.3 ñ 3.8 vs 31.1 ñ 5.8, mean percent of time spent in the open arms = 8.8 ñ 1.8 vs 12.5 ñ 2.2). The results, therefore, suggest that the pineal gland may play a modulatory role in the behavioral consequences of stress.

Attenuation of behavioral consequences of immobilization stress by intra-hippocampal microinjection of zimelidine

To investigate the role of hippocampal 5-HT neurotransmission on adaptation to aversive events, individually housed male Wistar rats (200-250 g) were immobilized for 2 h and tested 24 h later in an elevated plus-maze. Immediately after the restraint period they received bilateral microinjections into the dorsal hippocampus of either saline (0.5 microliters) or the nonselective 5-HT1 antagonist dl-propranolol (20 nmol/0.5 microliters). In a second experiment the first microinjection of saline or dl-propranolol was followed by a second microinjection of saline (0.5 microliters) or the 5-HT reuptake blocker zimelidine (20 nmol/0.5 microliters). Although dl-propranolol alone did not change exploration of the elevated plus-maze, it antagonized the increase in the percentage of open arm entries induced by zimelidine (26.0 +/- 4.1 vs 5.64 +/- 3.7 in controls). These results are compatible with the view that post-synaptic 5-HT1a receptors in the hippocampus mediate adaptive or coping responses to aversive events