Acute tianeptine treatment selectively modulates neuronal activation in the central nucleus of the amygdala and attenuates fear extinction.

Antidepressant drugs are commonly prescribed treatments for anxiety disorders, and there is growing interest in understanding how these drugs impact fear extinction because extinction learning is pivotal to successful exposure-based therapy (EBT). A key objective within this domain is understanding how antidepressants alter the activation of specific elements of the limbic-based network that governs such fear processing. Chronic treatment with the antidepressant tianeptine has been shown to reduce the acquisition of extinction learning in rats, yet the drug's acute influence on activation in prefrontal and amygdalar regions, and on extinction learning are not well understood. To assess its influence on cellular activation, rats were injected with tianeptine and Fos immunoreactivity was measured in these regions. Acute tianeptine treatment selectively altered Fos expression within subdivisions of the central nucleus of the amygdala (CEA) in a bidirectional manner that varied in relation to ongoing activation within the capsular subdivision and its prefrontal and intra-amygdalar inputs. This pattern of results suggests that the drug can conditionally modulate the activation of CEA subdivisions, which contain microcircuits strongly implicated in fear processing. The effect of acute tianeptine was also examined with respect to the acquisition, consolidation and expression of fear extinction in rats. Acute tianeptine attenuated extinction learning as well as the recall of extinction memory, which underscores that acute dosing with the drug could alter learning during EBT. Together these findings provide a new perspective for understanding the mechanism supporting tianeptine's clinical efficacy, as well as its potential influence on CEA-based learning mechanisms.

Comparative effects of melatonin, zolpidem and diazepam on sleep, body temperature, blood pressure and heart rate measured by radiotelemetry in Wistar rats.

RATIONALE: The role of melatonin (MLT) in mediating the sleep-wake cycle has been previously suspected of indicating that this substance could be a candidate for a new generation of hypnotics. OBJECTIVES: We investigated whether MLT acted as a sleep promoter or a modulator of sleep temporal timing related to cardiovascular and body temperature (Tb) adaptations to sleep induction. The pharmacological effects of MLT on sleep were compared with zolpidem (ZP) and diazepam (DZ). METHODS: The radiotelemetry system was used to record the electrocorticogram [slow wave sleep (SWS), paradoxical sleep (PS)], Tb, blood pressure and heart rate in six Wistar rats. DZ (3 mg/kg and 6 mg/kg), ZP (1, 3, 5 and 10 mg/kg) and MLT (2.5 and 5 mg/kg) were delivered intraperitoneally during light (L) and dark (D) periods. RESULTS: MLT increased the number of sleep cycles (L: 30%, D: 110%) and total duration (P<0.05) of PS (L: 70%, D: 150%). In return, ZP (10 mg/kg) presented no effect during L but increased total (40%) and mean duration (37%) of SWS during the D period. DZ modified mean duration of SWS (L: -27%, D: +26%) and increased total duration of SWS (+47%). ZP and DZ induced a more pronounced decrease in Tb than MLT but only DZ induced tachycardia and hypertension. CONCLUSIONS: We showed that MLT could not promote sleep and its cardiovascular adaptations despite hypothermia, but modulated the period of ultradian sleep cycles. DZ and ZP promoted sleep and induced hypothermia during the D period. Only DZ disrupted sleep architecture and induced adverse effects on cardiovascular parameters.

Effects of neonatal focal cerebral hypoxia-ischemia on sleep-waking pattern, ECoG power spectra and locomotor activity in the adult rat.

The aim of this study was to determine the influence of neonatal focal cerebral hypoxia-ischemia (HI) on sleep-waking pattern, electrocorticogram (ECoG) power spectra and locomotor activity (LA) in adult Wistar rats. Seven-day old pups were subjected to permanent unilateral ligation of the common carotid artery and transient hypoxia (8% O2). At 10 weeks of age, the extent of brain damages was evaluated by magnetic resonance imaging (MRI) and homogenous injured animals were selected before chronic implantation of radiotelemetry device. Using a single ECoG recording channel method, waking (W), paradoxical sleep (PS) and slow wave sleep (SWS) were continuously recorded for 72 h and they were semi-automatically analyzed off-line. We observed that neonatal HI triggers a cascade of events leading, in adult rats, to brain dysfunction characterized by an increase in SWS (55.0 vs. 40.2% in sham-operated rats, p<0.05) and a marked decrease in W phases duration (43.4 vs. 51.5%, p<0.05) while PS was almost suppressed in HI rats (1.6 vs. 8.3%, p<0.05). In addition, power spectral analysis of ECoG revealed significant (p<0.05) alteration in PS power density with a shift of the dominant frequency peak (5.0 to 7.5 Hz for HI and sham-operated rats, respectively). During the light period, we found that HI induced a pronounced reduction of LA (-30%, p<0.05). These results indicate that Wistar rats exposed to a neonatal unilateral cerebral HI present significant ECoG activity, sleep-waking pattern and behavioral disturbances when adults. However, it remains to establish whether such alterations can be prevented by neuroprotective agents.

Melatonin and seasonal reproduction: understanding the neuroendocrine mechanisms using the sheep as a model.

The mechanisms by which melatonin controls seasonal reproduction are poorly understood. The use of a large animal model, namely the sheep, has allowed progress in the understanding of these mechanisms, and is the subject of this review. Firstly, the contribution made by large animal models to demonstrating that melatonin acts in the hypothalamus and the identification of this hypothalamic target is reviewed. Secondly, the way in which large animal models have facilitated the demonstration of a specific mechanism of release of melatonin in the cerebrospinal fluid and, thus, raised the question of the route used by melatonin to reach its central targets is discussed. Finally, the human and agricultural relevance of the data presented is considered.