An endogenous ligand to the benzodiazepine receptor: preliminary evaluation of its bioactivity

Chromatographic separation of aqueous brain extracts yields a peptide containing fraction which competitively inhibits 3H-diazepam binding to its receptor. An intracerebral-ventricular injection of this isolated fraction results in altered responses in pharmacological and behavioral tests which are similar to those observed when diazepam is administered in the same fashion. The most pronounced effect was obtained in the conflict test. Changes observed in other tests, such as blocking pentylenetetrazole convulsions, altering motility or reducing hyperthermia, were also consistent with the actions of diazepam. At the dose used, neither diazepam nor the brain extract altered muscular co-ordination in two ataxia evaluations. Thus, the animals' performance in the other paradigms would not be adversely influenced by immobilization side-effects. The results reported here support the notion that an endogenous factor does exist in brain which can act like the benzodiazepine drugs when tested for bioactivity in animal studies.