Selective imidazoline I2 ligands do not show antidepressant-like activity in the forced swim test in mice.

Clonidine is an adrenergic agonist with high affinity for alpha2 adrenoceptors that also has affinity for imidazoline receptors. Clonidine has previously been shown to reduce immobility in the forced swim test (FST) in mice. In the present study, this effect was blocked by idazoxan (0.06 mg/kg s.c.) and by yohimbine (1.0 mg/kg s.c.) suggesting that clonidine's effects in this test are mediated via its action at alpha2 sites. Imidazoline I2 site ligands have been shown to inhibit monoamine oxidase and thus may also have antidepressant activity. Three compounds with selective affinity for I2 receptors (BU224, BU239, BDF 8082) were also tested in the FST. These compounds showed no activity either alone or in combination with a subthreshold dose of imipramine in the FST. These results suggest that I2 receptor ligands do not show antidepressant-like activity in the FST in mice. Furthermore the activity of the mixed alpha2/I1 agonist clonidine is most likely to be due to its action at alpha2 sites.

The relevance of chondroitin and keratan sulphate markers in normal and arthritic synovial fluid.

This study investigated the synovial fluid concentrations of glycosaminoglycan (GAG), keratan sulphate (KS) epitope 5D4 and chondroitin sulphate (CS) sulphation patterns in healthy volunteers and patients with osteoarthritis (OA) and rheumatoid arthritis (RA). Synovial fluids were collected from knee joints of healthy volunteers (n = 24), and patients with OA (n = 28) and RA (n = 29). Concentrations of GAG and the keratan sulphate epitope 5D4 were measured in 15 of the healthy volunteers, and all of the OA and RA synovial fluids. Total GAG was measured using a dye-binding method and 5D4 by an ELISA. The unsaturated CS disaccharides delta C4 and delta C6 were measured by capillary electrophoresis in all synovial fluids. The concentrations of GAG, 5D4 and delta C6 in the normal synovial fluid were higher but that of delta C4 lower than those of the disease groups. The delta C6:delta C4 ratios correlated with age (r = -0.437, P < 0.001) and the mean value was lower in females than males (2.92 compared with 5.22, P < 0.001). After allowing for age and sex, the delta C6:delta C4 ratio in the control group was significantly elevated (P < 0.001) compared to both OA and RA. The ratio was also related to proteoglycan markers (r = 0.383 for 5D4 and r = 0.357 for GAG). The finding that 5D4 and delta C6:delta C4 ratios are higher in synovial fluid from healthy volunteers compared to OA and RA suggests that they may be markers of the susceptibility of articular cartilage to early damage in arthritis.