PubMed · 10596265
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S Heinzl. 1999. [Is strong effectiveness dangerous?].. https://pubmed.ncbi.nlm.nih.gov/10596265/
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Previous studies have suggested that cannabis-like drugs produce mainly aversive and anxiogenic effects in Wistar strain rats, but rewarding effects in Lewis strain rats. In the present study we compared Fos expression, body temperature effects and behavioral effects elicited by the cannabinoid CB(1) receptor agonist CP 55,940 in Lewis and Wistar rats. Both a moderate (50 microg/kg) and a high (250 microg/kg) dose level were used. The 250 microg/kg dose caused locomotor suppression, hypothermia and catalepsy in both strains, but with a significantly greater effect in Wistar rats. The 50 microg/kg dose provoked moderate hypothermia and locomotor suppression but in Wistar rats only. CP 55,940 caused significant Fos immunoreactivity in 24 out of 33 brain regions examined. The most dense expression was seen in the paraventricular nucleus of the hypothalamus, the islands of Calleja, the lateral septum (ventral), the central nucleus of the amygdala, the bed nucleus of the stria terminalis (lateral division) and the ventrolateral periaqueductal gray. Despite having a similar distribution of CP 55,940-induced Fos expression, Lewis rats showed less overall Fos expression than Wistars in nearly every brain region counted. This held equally true for anxiety-related brain structures (e.g. central nucleus of the amygdala, periaqueductal gray and the paraventricular nucleus of the hypothalamus) and reward-related sites (nucleus accumbens and pedunculopontine tegmental nucleus). In a further experiment, Wistar rats and Lewis rats did not differ in the amount of Fos immunoreactivity produced by cocaine (15 mg/kg). These results indicate that Lewis rats are less sensitive to the behavioral, physiological and neural effects of cannabinoids. The exact mechanism underlying this subsensitivity requires further investigation.
Nociceptin/orphanin FQ (NC) and its receptor (OP(4)) have been implicated in the regulation of various functions including nociception. [Nphe(1)]NC(1-13)NH(2) (Nphe) is a selective OP(4) antagonist which prevents the pronociceptive effects of supraspinal NC and causes per se a naloxone-insensitive antinociceptive effect. In the present study, we tested Nphe in wild type (WT) and OP(4) receptor knock out mice and found that a clear antinociceptive effect of the antagonist was evident only in WT mice. Moreover, we evaluated, over 5 days of treatment, the antinociceptive effects of Nphe in comparison with those of DAMGO and found that tolerance develops to the effects of the opioid receptor agonist but not to Nphe. These data demonstrate that the antinociceptive action of Nphe is due to the block of OP(4) receptors and that no tolerance develops to this kind of antinociception.
Small dorsal root ganglion (DRG) neurons are characterized by sensitivity to capsaicin. In acutely isolated rat DRG neurons, the effect of neomycin, one of the aminoglycoside antibiotics, on capsaicin-evoked current and voltage responses was examined using whole-cell patch-clamp recording. We showed for the first time that neomycin dose-dependently inhibited capsaicin-evoked currents with half-maximal inhibitory concentration at 130.60 microM (n=70). Under current-clamp condition, depolarization and firing rate evoked by capsaicin became weakened when neomycin was perfused to the neurons (n=10). Neomycin had no significant effect on the resting potentials of DRG neurons. These results suggest that neomycin could inhibit capsaicin-sensitive responses in small DRG neurons, which may contribute to neomycin-induced peripheral analgesia.