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The exposure of rats for 2 min to an open field, to a small box, or to inhibitory avoidance training in the small box was followed by a mild analgesia measured by the tail-flick method. The analgesia was observed as soon as 10 s after the exposure and lasted between 10 and 30 min. It was not observed in animals previously made familiar with the test situation, and it was reversed by the administration of naltrexone (0.1 mg/kg). The data suggest that novelty per se is a sufficient stimulus to activate an opioid-mediated analgesic stimulus.

1. Proline endopeptidase (E.C.3.4.21.26) is an enzyme which cleaves several peptides at the carboxyl side of proline residues. Because brain contains relatively large amounts of this enzyme and because of its specificity it has been suggested that it plays a role in the metabolism of neuropeptides, acting both on their processing and their degradation. 2. Since the final steps of neuropeptide processing occur in the synaptic vesicles and the degradation of most of these peptides is believed to occur in the synaptic cleft, we studied the distribution of proline endopeptidase activity in sub-fractions of rat hypothalamus. 3. Proline endopeptidase activity is present in synaptosomal fractions and is released by hypo-osmotic shock. Its specific activity is higher in the synaptoplasma than in synaptic membranes or vesicles (7.98 vs 0.18 and 0.24 nmol min-1 mg protein-1 carbobenzoxy-glycyl-prolyl-sulfamethoxazole hydrolysis). 4. Inhibitory avoidance training, a situation which releases hypothalamic vasopressin and beta-endorphin, both in vitro substrates, did not affect the specific or total activity of proline endopeptidase in synaptosomal plasma membranes.