The task was carried out in a small, dimly lit room

The task was carried out in a small, dimly lit room

inistration in male rats led to visceral hyperalgesia in response to colorectal distension, accompanied by increased AEA, decreased CB1 expression, and increased TRPV1 expression in dorsal root ganglia. Co-treatment with the corticoid receptor antagonist RU-486 prevented these changes. In summary, preclinical rodent studies indicate that acute glucocorticoid administration enhances the activity of eCBs. The clinical phenomenon of acute “corticosteroid mania”may have a cannabimimetic component. Chronic exposure to glucocorticoids downregulates the eCB system, a scenario consistent with chronic stress, which we review below. Opiates. Naloxone, a m-opioid receptor antagonist, inhibited THC-induced Fos immunoreactivity in several regions of the rat central nervous system, including the ventral tegmental area, hypothalamus, caudate-putamen, and periaqueductal grey. Conversely, naloxone and THC had an additive effect on Fos immunoreactivity in the amygdala, stria terminalis, insular cortex, and paraventricular nucleus of the thalamus. Short-term co-administration of morphine with THC caused an upregulation of CB1 protein in the spinal column of rats, far greater than THC or morphine given alone. A rodent study of chronic but voluntary intake of opiates enhanced CP55,940 binding in the amygdala and ventral tegmental area, plus a marked increase in cannabinoidstimulated GTPcS binding in the nucleus accumbens, caudate putamen, and amygdala. Superperfusion of ex vivo rat nucleus accumbens slices with 4-aminopyridine and NMDA released glutamate and GABA, respectively, and either morphine or the CB1 agonist HU210 predictably inhibited these responses. Combining HU210 and morphine caused a c-Met inhibitor 2 site synergistic inhibition of GABA release, but a non-additive response in glutamate release. Chronic morphine exposure in rats caused a reduction in hippocampal and cerebellar CB1 density measured with CP55,940, and a strong reduction in CP55,940-stimulated GTPcS binding; 2-AG contents were also reduced. Another rat study showed that chronic morphine exposure caused variable, regionally-specific modulations in CP55,940 binding and CB1 mRNA levels; CB1 upregulated in some regions and dowregulated in other PubMed ID:http://www.ncbi.nlm.nih.gov/pubmed/19632393 regions. In human CB1-transfected HEK293 cells, morphine induced a desensitization of the m-opioid receptor and heterologous desensitization of CB1, demonstrated by a reduction in WIN55212-2-induced i release. mopioid receptor knockout mice showed a dramatic reduction in WIN55212-2-stimulated GTPcS binding. In human SHSY5Y neuroblastoma cells, sequential activation of CB1 and dopioid receptor produced synergistic elevations of intracellular Ca2+, a response that each receptor alone did not trigger in an efficacious way. In behavioral studies, heroin reinstated “drug-seeking”behavior for WIN55,212-2 in rats. Morphine did the same for THC in monkeys. The rewarding effects of THC, measured by conditioned place-preference, were reversed by naloxone in rats. In rats trained to discriminate THC, morphine administration markedly potentiated the THC discriminative PubMed ID:http://www.ncbi.nlm.nih.gov/pubmed/19632179 stimulus. Morphine or codeine potentiated THC-induced antinociception and analgesia in mice and rats; inactive doses of the drugs in combination produce potent, synergistic analgesia. Synergistic analgesia was confirmed in an isobolographic analysis. Historically this is the first isobolographic analysis of a cannabinoid since the days Walter Siegfried Loewe, who invented the isobologram to test drug combinations f

Proton-pump inhibitor

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