ETHOPHARMACOLOGICAL ANALYSIS OF NALOXONE-PRECIPITATED MORPHINE-WITHDRAWAL SYNDROME IN RATS - A NEWLY DEVELOPED ETHO-SCORE

The intensity of opiate withdrawal syndrome in rats is usually quantif ied on the basis of selected physical signs or global scores. However, the selection criteria of signs and scores have not been subjected to an ethological discussion, hence they appear to be somewhat arbitrary . The objectives of this study were thus: i) to analyse the rat's beha viour during the naloxone-precipitated morphine withdrawal syndrome, i i) to evaluate the validity of classic methods, and iii) to design a n ew ''etho-score''. Ten rats were implanted with morphine pellets (75 m g x 2, SC), all receiving different naloxone doses following a within- subject design (0, 0.01, 0.05, 0.1, 0.5, 1 mg/kg SC). Twenty unexperie nced rats and 20 with placebo pellets were injected with either saline or naloxone. Behaviour was videotaped and later analysed by computer- based ethological techniques. The ethogram encompassed 16 patterns dis played by rats during morphine withdrawal. Frequency, duration and lat ency of each pattern was measured, and a cluster analysis allowed disc erning the structure of behaviour. Several physical signs and the Gell ert-Holtzman score were also evaluated. The data revealed that writhin g responses linearly changed in a dose-related fashion, and masticatio n was also enhanced after naloxone. Wet-dog shakes and jumping changed following an U-shaped curve. Significant changes in weight loss were found to be dose-dependent, and highly correlated to diarrhea. Learnin g effects were found to reliably affect exploration, writhing response s and some physical signs. The Gellert-Holtzman score was gradually en hanced after naloxone, being affected by learning as well. Naloxone af fected lying and self-care responses in placebo rats. To sum up, the d ata indicated that: i) classic signs are useful, although most of them are disrupted by high naloxone or affected by learning effects, ii) t he Gellert-Holtzman score was validated in this study, and iii) mastic ation and weight loss are good indicators of naloxone-precipitated mor phine withdrawal, representing the basis of an ''etho-score'' which is herein proposed.