2--hydroxy-5-9-dimethyl-2-allyl-6-7-benzomorphan and Body-Weight

Sigma (sigma) sites are a type of nonopiate receptor whose role has been associated with several behaviours, including anxiety, depression, analgesia, learning processes and psychosis. Although there are several known sigma receptor types, only the type I receptor (sigma 1) has been cloned. To uncover the in vivo relevance of sigma-receptors, we have generated knockout mice for sigma 1. Despite the broad expression pattern found for the sigma 1-gene, homozygous mutant mice are viable, fertile and do not display any overt phenotype, compared with their wild-type litter-mates, in mixed genetic backgrounds. However, a significant decrease in the hypermotility response has been measured in knockout mice upon challenge with (+)SKF-10 047, in agreement with the involvement of sigma 1-receptors in the induction of psychostimulant actions. The activity of sigma 2-receptors seems to be unaffected in sigma 1-mutant mice. These knockout mice could contribute to better understand the in vivo role of sigma-receptors.

Topics: Animals; Animals, Newborn; Antidepressive Agents; Antipsychotic Agents; Behavior, Animal; Binding, Competitive; Blotting, Northern; Blotting, Southern; Blotting, Western; Body Weight; Cells, Cultured; Embryo, Mammalian; Endorphins; Heterozygote; Hyperkinesis; In Situ Hybridization; Mice; Mice, Knockout; Narcotic Antagonists; Oligonucleotides, Antisense; Pentazocine; Peptide Fragments; Phenazocine; Phenotype; Radioligand Assay; Receptors, sigma; Sigma-1 Receptor; Time Factors

The current study investigated the effects of acute and chronic administration of (+)-SKF 10,047 on body temperature in rats. The effect of phencyclidine on body temperature in chronically (+)-SKF 10,047-treated rats was also investigated. The acute administration of (+)-SKF 10,047 at doses of 5 to 40 mg/kg s.c. did not alter body temperature; however, 80 mg/kg produced hypothermia. In contrast, chronic administration of (+)-SKF 10,047 (5-20 mg/kg) produced dose-dependent hyperthermia when tested on day 7 and 10 of chronic treatment. Moreover, sensitization to the hyperthermic effects occurred as the degree of hyperthermia was greater on day 10 compared to day 7. Phencyclidine (20 mg/kg s.c.) produced hypothermia in rats chronically treated with saline for 13 days, but hyperthermia in rats chronically treated with 20 mg/kg of (+)-SKF 10,047 for the same duration. The hyperthermic effect of chronic (+)-SKF 10,047 treatment is similar to the previously reported dose-dependent hyperthermia in chronically phencyclidine-treated animals. The cross-sensitization of chronically (+)-SKF 10,047-treated rats to the hyperthermic effects of phencyclidine supports the hypothesis that there may be common mechanisms underlying the chronic effects of these drugs on body temperature.

Topics: Animals; Body Temperature; Body Weight; Dose-Response Relationship, Drug; Drug Interactions; Injections, Subcutaneous; Male; Phenazocine; Phencyclidine; Rats; Rats, Inbred Strains; Receptors, Opioid; Receptors, sigma; Stereoisomerism