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C M Padovan

Publications and source records attributed to C M Padovan.

7 recordsLinked to original sources

Antidepressant-like effects of NMDA-receptor antagonist injected into the dorsal hippocampus of rats.

Exposure to uncontrollable stressors causes behavioral changes that have been related to depressive states in humans. Poststress intrahippocampal administration of amino-7-phosphonoheptanoic acid (AP-7), a glutamate NMDA-receptor antagonist, attenuated the restraint-induced decreased exploration of an elevated plus maze 24 h later. The objective of the study was to test if this treatment would also attenuate the increased immobility seem in the forced swim test (FST) due to preexposition to this stressful situation. Male Wistar rats with cannulae aimed at the dorsal hippocampus were submitted to 15 min of forced swimming and tested 24 h later. They received bilateral intrahippocampal injections of AP-7 (10 nmol) either before or after the pretest swimming session or before the test. Poststress treatment increased latency to display the first episode of immobility and tended to reduce total immobility time. The drug was ineffective when given before stress or before test and in nonstressed animals. This suggests that glutamate NMDA receptors located in the dorsal hippocampus are involved in the behavioral changes observed in the FST.

2-Amino-5-phosphonovalerate↗

Expression of neuronal nitric oxide synthase mRNA in stress-related brain areas after restraint in rats.

The objective of the present study was to investigate the expression of neuronal nitric oxide synthase (nNOS) mRNA in stress-related areas after restraint. Male Wistar rats (n=4-6/group) submitted to 2 h of restraint during one (acute) or seven (chronic) days were sacrificed 24 h after the last restraint period. In situ hybridisation was performed with oligonucleotide probes radiolabeled with (35)S. Acute restraint induced a significant increase in nNOS mRNA in the paraventricular hypothalamic nucleus (PVN), medial parvocellular part, dorsolateral periaqueductal grey (DLPAG) and medial amygdaloid nucleus, but not in the hippocampal formation. This effect persisted after chronic restraint in the PVN and DLPAG. These results suggest that restraint stress induces changes in gene expression of nNOS in areas related to stress reactions.

Amygdala↗

Behavioral effects in the elevated plus maze of an NMDA antagonist injected into the dorsal hippocampus: influence of restraint stress.

The objective of the study was to investigate the influence of restraint stress on the effects of 2-amino-7-phosphonoheptanoic acid (AP7), an NMDA receptor antagonist, injected into the hippocampus of rats submitted to the elevated plus maze (EPM). Male Wistar rats with cannulas aimed to the dorsal hippocampus were forced immobilized for 2 h. Twenty four hours later they received bilateral injections of saline or AP7 (10 nmol/0.5 microl), and were tested in the EPM. In another experiment the animals received the treatment immediately before or after the restraint period, and were tested in the EPM 24 h later. AP7 had no effect in any anxiety measure in non-stressed rats. In stressed animals the drug increased the percentage of open arm entries when injected before the test in the EPM. When administered immediately after the restraint period, AP7 increased the percentage of time spent in the open arms and tended to do the same with the percentage of entries in these same arms. The results suggest that interference with hippocampal NMDA receptors modify the anxiogenic effect of restraint stress in an EPM.

2-Amino-5-phosphonovalerate↗

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.

Analysis of Variance↗

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 +/- 2.3 vs 18.0 +/- 2.1, mean percent of time spent in the open arms = 11.8 +/- 2.1 vs 6.8 +/- 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 +/- 3.8 vs 31.1 +/- 5.8, mean percent of time spent in the open arms = 8.8 +/- 1.8 vs 12.5 +/- 2.2). The results, therefore, suggest that the pineal gland may play a modulatory role in the behavioral consequences of stress.

Animals↗

Hippocampal 5-HT receptors and consolidation of stressful memories.

It has been suggested that postsynaptic 5-HT1A receptors in the hippocampus, innervated by 5-HT neurons localized in the median raphe nucleus, mediate adaptive or coping responses to aversive events and that dysfunction of this system is related to symptoms of depression. To test this hypothesis we investigated the expression of c-fos mRNA in animals submitted to immobilization stress. The results showed that c-fos mRNA expression is significantly increased in the dentate gyrus and CA1-CA3 regions of the hippocampus after 30 min of forced restraint, suggesting that this structure is activated during stress. To investigate the role of 5-HT neurotransmission in the hippocampus on adaptation to aversive events we immobilized rats for 2 h and tested them 24 h later in an elevated plus-maze. Our results showed that the previous restraint period decreases exploration of open arms in the maze. This effect was reversed by bilateral microinjection of zimelidine (20 and 100 nmol), a 5-HT re-uptake blocker, or 8-OH-DPAT (3 nmol), a 5-HT1A agonist, into the dorsal hippocampus immediately after restraint. These results are compatible with the idea that postsynaptic 5-HT1A receptors located in the hippocampus participate in the development of tolerance to aversive events.

Animals↗

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.

Animals↗