Melanocortins protect against brain damage and counteract cognitive decline in a transgenic mouse model of moderate Alzheimer׳s disease.

We previously reported that melanocortins induce neuroprotection in experimental acute and chronic neurodegenerative conditions, including Alzheimer׳s disease (AD) of mild severity. Here we investigated whether melanocortins afford neuroprotection and counteract cognitive decline in AD with a medium level of severity by using 24 week-old (at the start of the study) APPSwe transgenic mice (Tg2576). Saline-treated (days 1-50) control Tg2576 mice showed an impairment in spatial learning and memory, associated (at day 50, end of the study) with hippocampus at low levels of the synaptic activity-dependent gene Zif268, relevant brain changes such as cerebral cortex/hippocampus increased level of β-amyloid (Aβ) deposit, and neuronal loss, in comparison with wild-type animals.

Up-regulation of the canonical Wnt-3A and Sonic hedgehog signaling underlies melanocortin-induced neurogenesis after cerebral ischemia.

In experimental cerebral ischemia, melanocortin MC4 receptor agonists induce neuroprotection and neurogenesis with subsequent long-lasting functional recovery. Here we investigated the molecular mechanisms underlying melanocortin-induced neurogenesis. Gerbils were subjected to transient global cerebral ischemia, then they were treated every 12 h, and until sacrifice, with 5-bromo-2'-deoxyuridine (BrdU; to label proliferating cells), and the melanocortin analog [Nle(4),d-Phe(7)]α-melanocyte-stimulating hormone (NDP-α-MSH) or saline.

The antinociceptive effect of acetylsalicylic acid is differently affected by a CB1 agonist or antagonist and involves the serotonergic system in rats.

Aims: Combinations of non-steroidal anti-inflammatory drugs (NSAIDs) and cannabinoids are promising because of their potential synergistic effects in analgesia, resulting in a reduction in dosage and minimizing adverse reactions. The analgesic effect of acetylsalicylic acid (ASA), probably due to a central mechanism, also implicates changes in the central monoaminergic system. Therefore, we decided to evaluate the antinociceptive interaction between the CB(1) receptor agonist, HU210, and ASA in tests involving central pain in rats as well as the implication of the central serotonergic system thereon.

Glutamate-mediated astrocyte-to-neuron signalling in the rat dorsal horn.

By releasing neuroactive agents, including proinflammatory cytokines, prostaglandins and neurotrophins, microglia and astrocytes are proposed to be involved in nociceptive transmission, especially in conditions of persistent, pathological pain. The specific action on dorsal horn neurons of agents released from astrocytes, such as glutamate, has been, however, poorly investigated. By using patch-clamp and confocal microscope calcium imaging techniques in rat spinal cord slices, we monitored the activity of dorsal horn lamina II neurons following astrocyte activation.

Differential involvement of opioidergic and serotonergic systems in the antinociceptive activity of N-arachidonoyl-phenolamine (AM404) in the rat: comparison with paracetamol.

It is recognized that paracetamol undergoes a metabolic transformation to N-arachydonylphenolamine (AM404), a CB(1) receptor ligand and anandamide uptake inhibitor. Using hot-plate and paw pressure tests, we decided to establish whether AM404 may act through opioidergic and serotonergic mechanisms. Thus, we pretreated rats with opioid mu(1) (naloxonazine) and kappa (MR2266) or 5-HT(1A) (NAN-190), 5-HT(2) (ketanserin), and 5-HT(3) (ondansetron) receptor antagonists.

The analgesic activity of paracetamol is prevented by the blockade of cannabinoid CB1 receptors.

The mechanism of the analgesic activity of paracetamol (acetaminophen), one of the most widely used drugs for the treatment of pain, is still not clear. Here we show that in rats, using the hot plate test, the analgesic effect of paracetamol is prevented by two antagonists at cannabinoid CB1 receptors (AM281 and SR141716A) at doses that prevent the analgesic activity of the cannabinoid CB1 agonist HU210. Our present results suggest that paracetamol-induced antinociception involves the cannabinoid system.

Acute noise stress analgesia in relation to 5-HT2 and mu-opioid receptor changes in the frontal cortex of young mice.

A number of studies have reported that exposure to stress provoked behavioural changes, including analgesia, in rodents. Differences have been observed in these responses to different types of stress and a link between hormones and neurotransmitters proposed. We studied the effect of acute noise stress on nociception and the possible changes in the serotonergic and opioidergic systems in young mice of both sexes.

Nociceptin/orphanin FQ prevents the antinociceptive action of paracetamol on the rat hot plate test.

Nociceptin/orphanin FQ (N/OFQ) is involved in many behavioural patterns; in particular, it exerts a modulating effect on nociception. Like other proposed antiopiates, nociceptin/orphanin FQ has been shown to have analgesic, hyperalgesic as well as antianalgesic properties. Among the various effects proposed on nociceptive sensitivity at supraspinal level, the antagonistic activity toward morphine analgesia seems to be of interest.

Nitroglycerin induces hyperalgesia in rats--a time-course study.

Nitroglycerin is a nitric oxide (NO) donor which activates nuclei involved in nociceptive transmission following systemic administration. The effect of nitroglycerin on the nociceptive threshold was studied in rats by means of two experimental tests that explore different modalities of pain: the tail-flick test and the formalin test. Nitroglycerin induced a significant reduction in the latency of the tail flick 2 and 4 h after its administration.

Central antinociceptive activity of acetylsalicylic acid is modulated by brain serotonin receptor subtypes.

Male Wistar rats were treated with ondansetron (1 and 2 mg/kg s.c.), ketanserin (0.