Brain contents of substance P, diazepam-binding inhibitor, and neuropeptide Y in high- and low-anxiety inbred rats during stress

Abstract

The content of substance P in the hippocampus, hypothalamus, and midbrain of WAG/G rats surpassed these in Fischer-344 rats. After a 15-min stay in a shuttle box, the level of substance P in the hypothalamus and especially in the hippocampus decreased only in WAG/G rats. The content of diazepam-binding inhibitor in the hippocampus and midbrain of WAG/G rats was higher than in Fischer-344 rats. Stress increased the content of diazepam-binding inhibitor only in Fischer-344 rats. Midbrain content of neuropeptide Y in intact and stressed WAG/G rats was significantly lower than in Fischer-344 rats. There were no interstrain differences in the initial hypothalamic levels of neuropeptide Y between WAG/G and Fischer-344 rats. However, 15-min stress in the shuttle box increased hypothalamic content of neuropeptide Y only in Fischer-344 rats. Thus, high-anxiety rats are characterized by a low density of benzodiazepine receptors, decreased levels of substance P and diazepam-binding inhibitor, and high brain content of neuropeptide Y. Key Words: anxiety," substance P; diazepam-binding inhibitor; neuropeptide Y; stress," inbred ratsSome peptide systems of the brain are involved in the mechanisms of anxiety. Octapeptide cholecystokinin enhances anxiety in rats [5], while neuropeptide Y (NPY) reduces it [6]. Substance P (SP) causes similar antistress and anxiolytic effects [1]. Moreover, a dipeptide inhibiting diazepam binding (diazepam-binding inhibitor, DBI) was found in mammalian brain. DBI possesses a considerable anxiogenic activity, and immunization against this dipeptide increases the resistance to stress [2].

Differences in genetic predisposition to high anxiety in two inbred rat strains: role of substance P, diazepam binding inhibitor fragment and neuropeptide Y

“…Fischer-344/N rats, which had higher measured levels of anxiety than WAG/G rats both in the present and in past experiments, not only have a lower density of brain benzodiazepine receptors than WAG/G rats, but also have lower brain levels of substance P and diazepam-bindinginhibitor fragment (DBI) and higher levels of neuropeptide Y (Lyupina et al 1999;Sudakov et al 1999). It is possible that decreased brain levels of substance P may be one determinant of high levels of anxiety.…”