PubMed · 16323708
The source did not provide an abstract. Follow the original record for more information.
Explore connections, maps & timelines
Jonathan D Moreno. Keeping pain in perspective.. https://pubmed.ncbi.nlm.nih.gov/16323708/
Cite the original work for its findings. Save a collection to share your selection of sources.
KEEP EXPLORING
In the present study, dopamine release was monitored during cannabinoid self-administration in rats to achieve a detailed understanding of the way in which dopamine mediates the reinforcing effects of cannabinoids. Extracellular dopamine levels were measured in the shell of the nucleus accumbens of either Lister Hooded or Long Evans rats trained to self-administer the cannabinoid CB1 receptor agonist WIN 55,212-2. A significant relationship between extracellular dopamine levels and bar-pressing rates was observed in both strains, as the dopamine content appreciably increased in respect to basal values during cannabinoid intake. Importantly, dopamine was not modified when trained rats were shifted to vehicle self-administration suggesting that an enhanced activity of the mesolimbic dopamine pathway underlies cannabinoid-taking behaviour.
High-throughput screening of the UCB sample collection identified the piperidinyl-sulfonyl benzoic ester 1 as a novel agonist for CB(1) receptor with nanomolar affinity. We report here the pharmacological profile of compound 1 as well as preliminary biological activities in pain model. Diverse close analogs of 1 were purchased and the structure-affinity relationships among this novel class are discussed.
RATIONALE: Clinical observations have shown that pain sensitivity is altered in some schizophrenic patients. OBJECTIVES: To study alterations in pain sensitivity, the ketamine model in schizophrenia research was employed. MATERIALS AND METHODS: Rats were subchronically injected with the dissociative anaesthetic ketamine (Ket, ten injections of 30 mg/kg, one injection per day over a period of 10 days). Two weeks after treatment completion, the animals' pain sensitivity was assayed in the hot plate test and they were subjected to electrical stimulation of the tail root. In addition, the effect of morphine was studied. RESULTS: In group-housed animals, there was no difference between Ket-injected animals and control rats as measured in both nociceptive tests. In singly housed Ket-injected rats, pain threshold was increased in the electrical stimulation test. This suggests that stress due to single housing might be essential for modifications of pain sensitivity. Moreover, the antinociceptive effect of morphine was modified after single housing. Interestingly, the effect of morphine on locomotor activity was similar in both groups. In group-housed rats, mu receptor binding was unchanged in the frontal cortex, whereas Ket-injected animals had decreased levels in the hippocampus. In singly housed animals, mu receptor binding in Ket-injected rats increased in the frontal cortex and decreased in the hippocampus. (35)S-GTPgamma-S binding increased in the frontal cortex in both singly housed groups, but remained unchanged in the hippocampus. CONCLUSIONS: The data suggest that the ketamine model might be useful for studying altered pain sensitivity in schizophrenia. Moreover, the data suggest that modifications in mu opioid receptor binding contribute to this phenomenon.