Hyperthermic responses to central injections of some peptide and non-peptide opioids in the guinea-pig

Abstract

Intracerebroventricular administration of prototype non-peptide opioid receptor (μ, κ, σ) agonists, morphine, ketocyclazocine and N-allyl normetazocine (SKF 10,047) and an agonist at both κ and σ receptors, pentazocine, induced hyperthermia in guinea-pigs. Similar administration of peptide opioids like β-endorphin (BE), methionine enkephalin (Met-E), leucine enkephalin (Leu-E) and their synthetic analogues d-ala 2-methionine-enkephalinamide ( d-ala 2-Met-E) and d-ala 2-leucine-enkephalinamide ( d-ala 2-Leu-E) also caused hyperthermia. Of the three anion transport systems (iodide, hippurate and liver-like) present in the choroid plexus, only the liver-like transport system seems to be important to central inactivation of β-endorphin, d-ala 2-Met-enkephalin and d-ala 2-Leu-enkephalin since iodipamide (an inhibitor of the liver-like transport system) augmented the hyperthermia. Prostaglandins (PG) and norepinephrine (NE) were not involved in peptide- and non-peptide opioid-induccd hyperthermia because a prostaglandin synthesis inhibitor, indomethacin, and an α-adrenergic receptor blocker, phenoxybenzamine, had no thermolytic effect. Likewise cAMP was not required since a phosphodiesterase inhibitor, theophylline. did not accentuate the hyperthermia due to administration of peptide and non-peptide opioids. Naloxone-scnsitive receptors were involved in the induction of hyperthermia by morphine and β-endorphin since naloxone attenuated the effect. In contrast, the hyperthermic responses to ketocyclazocine, SKF 10,047, pentazocine, Met-enkephalin, Leu-enkephalin, d-ala 2-Met-enkephalin and d-ala 2-Leu-enkephalin were not antagonized by naloxone. Lack of antagonism of naloxone on pyrogen, arachidonic acid. PGE 2, dibutyryl cAMP and NE-induced hyperthermia indicates that endogenous opioid peptides are not likely to be central mediators of the hyperthermia induced by these agents.