Neurochemical actions of ethylketocyclazocine and ketocyclazocine in different regions of rat brain.

The effects of ethylketocyclazocine (EKC) and ketocyclazocine (KC), benzomorphan derivatives proposed as kappa opioid receptor agonists, were studied by measuring changes in the levels of dopamine (DA), noradrenaline (NA), 5-hydroxytryptamine (5-HT), and their major metabolites, DOPAC, HVA, MHPG-SO4, 5-HIAA, in different regions of rat brain. Doses ranging from 1 to 10 mg/kg were tested. EKC decreased the levels of DOPAC and HVA in striatum, and increased DA concentrations, EKC markedly increased the levels of MHPG-SO4 in hypothalamus, but not in cortex, midbrain and pons-medulla. There was a non-significant decrease in NA concentrations. EKC increased the levels of 5-HIAA in hypothalamus and also in cortex, midbrain and pons-medulla, while the levels of 5-HT were increased. On the whole, similar neurochemical effects were observed after KC administration. These data were discussed in relation to the behavioral actions caused in rats by EKC and KC, including the increase in food intake, and they raise the possibility that the hypothalamic noradrenergic system participate in feeding behavior of these drugs.