TOLERANCE TO THE HYPOTHERMIC BUT NOT TO THE ANALGESIC EFFECT OF [D-TRP(11)]NEUROTENSIN DURING THE SEMICHRONIC INTRACEREBROVENTRICULAR INFUSION OF THE PEPTIDE IN RATS

The peptidase-resistant derivative of neurotensin, [D-Trp11]neurotensi n, has been continuously infused intracerebroventricularly (75 ng/h) w ith an osmotic minipump for 10 days. On several days during this infus ion the locomotor activity, the body temperature. the food intake, the body weight, and the nociceptive response in the plantar test were me asured. A nonsignificant decrease of body temperature and a sustained analgesic effect were observed at each time considered. The response t o a test dose of [D-Trp11]neurotensin (75 ng per rat) injected intrace rebroventricularly at the 10th day of the chronic infusion revealed a complete tolerance to its hypothermic effect. Thus, it appears that th e analgesic effect of [D-Trp11]neurotensin is independent of a hypothe rmic or an incapacitating effect of the peptide and does not give rise to tolerance after a 10-day continuous administration, in contrast to the hypothermic effect.