The Postnatal Leptin Surge Supports Immune Cell Function in Rats.

BACKGROUND: Leptin plays an important role in the regulation of the immune response. There is a physiological surge of leptin in rodents during the neonatal period, which has mainly been studied in the context of brain development. However, little is known about the effects of this neonatal leptin surge on immunity. Therefore, we investigated whether blocking this leptin surge could affect several immune functions. METHODS: Male and female rats were injected subcutaneously with 5 mg/Kg/day of rat pegylated super leptin antagonist during the neonatal period (PND5-9). On the peripubertal period, relevant functions as well as cytokine release by spleen leukocytes were studied in these animals. RESULTS: The results showed that the animals significantly display an impaired anti-tumor NK activity and chemotactic and proliferation capacity of lymphocytes in response to mitogens. In addition, several cytokine concentrations, released under mitogen-stimulated conditions, were also altered. CONCLUSION: In conclusion, the neonatal leptin surge seems to be involved in the establishment of an adequate immune response and cytokine profile, which are crucial for the maintenance of a healthy life.

Unconditioned and conditioned anxiogenic effects of the cannabinoid receptor agonist CP 55,940 in the social interaction test.

In spite of the addictive properties of cannabinoids, under certain circumstances, they can evoke strong anxiogenic and aversive responses in humans and in animal tests of anxiety. Effects of different doses of CP 55,940 (10, 20, and 40 microg/kg) were tested in the low-light, familiar (LF) apparatus test condition of the social interaction test. The 40-microg/kg dose of CP 55,940 significantly decreased the time spent in social interaction, indicating an anxiogenic effect. This dose also had an independent effect of reducing locomotor activity. In rats tested undrugged 24 h after testing with 40 microg/kg, there was a significant anxiogenic effect, indicating conditioned anxiety. The group of rats injected with 40 microg/kg immediately after the social interaction test showed an unexpected significant anxiolytic effect when tested undrugged 24 h later. In an additional experiment, rats were tested in the high-light, familiar (HF) apparatus test condition after 10 or 40 microg/kg, and only those that were tested after 40 microg/kg showed an anxiogenic effect on the test day and a conditioned anxiogenic effect when tested undrugged 24 h later. Once again, those injected with 40 microg/kg after the social interaction test displayed an anxiolytic effect when tested undrugged 24 h later. We provide the first evidence for unconditioned and conditioned anxiogenic-like responses to a cannabinoid agonist in the social interaction test.

Neuroprotection by the cannabinoid agonist WIN-55212 in an in vivo newborn rat model of acute severe asphyxia.

This study was designed to evaluate the neuroprotective effect of the cannabinoid agonist WIN-55212 after inducing acute severe asphyxia in newborn rats. The left common carotid artery was ligated in anaesthetised 7-day-old Wistar rats, which were then asphyxiated by inhaling 100% nitrogen for 10 min. Pups recovering from asphyxia were s.c. administered vehicle (n=23), WIN-55212 (0.1 mg/kg, n=18), or WIN-55212 plus the CB1 receptor antagonist SR141716 (3 mg/kg, n=10). Pups undergoing a sham operation served as controls (n=12). Coronal sections of the brain were obtained on the 14th day after surgery and observed under light microscope after Nissl or Fluoro-Jade B (FJB) staining, to respectively quantify surviving or degenerating neurones in the CA1 area of the hippocampus and parietal cortex. Acute asphyxia led to early neurone loss amounting to 19% in the hippocampus and 29% in the cortex (both ANOVA P<0.05 vs. control). Delayed neurone loss occurred in the proportions 13% in the hippocampus and 20% in the cortex (both ANOVA P<0.05 vs. control). Neuronal loss was fully prevented by WIN-55212 administration. Co-administration of SR141716 failed to modify the protective effect of WIN-55212 on early neuronal death, but abolished the WIN-55212-induced prevention of delayed neuronal death. We conclude that when administered after acute severe asphyxia in newborn rats, WIN-55212 shows a neuroprotective effect, reducing both early and delayed neurone loss. This effect is achieved through two parallel CB1-dependent and -independent mechanisms.

Antinociceptive, behavioural and neuroendocrine effects of CP 55,940 in young rats.

The peripubertal period appears to be critical in relation to the abuse of cannabinoids and opioids in humans. However there is little information about the acute effects of cannabinoids and their interactions with opioids in young experimental animals. We have studied the effects of the cannabinoid agonist CP 55,940 (0.1, 0.2, 0.4 and 0.6 mg/kg) on the nociceptive responses (tail immersion test) and holeboard activity of 40-day-old rats, and the involvement of the CB(1) receptor (antagonism by SR 141716A, 3 mg/kg). The implication of the opioid system was evaluated using the opioid antagonist naloxone (1 mg/kg) and a combined treatment with subeffective doses of CP 55,940 (0.1 mg/kg) and morphine (1 mg/kg). The effects of CP 55,940 on the serum corticosterone levels (radioimmunoassay) and on the dopamine and DOPAC contents of discrete brain regions (high-performance liquid chromatography) were also assessed. The antinociceptive effect of CP 55,940 was of a similar magnitude at all the doses used. The results show the involvement of the CB(1) receptor. The cannabinoid agonist significantly depressed the holeboard activity in a dose-dependent manner. The results indicate that the CB(1) receptor is involved in the effects on motor activity but not in the effects on the exploratory activity. The behavioural effects of CP 55,940 were modulated by morphine. The cannabinoid agonist (0.6 mg/kg) induced a CB(1)-mediated increase in the serum corticosterone levels, but no effect on the dopaminergic systems of either the striatum or the limbic forebrain was found.