Physiology &Behavior, Vol. 28, pp. 39--43.PergamonPress and Brain Research Publ., 1982.Printed in the U.S.A. Tail Pinch Behavior and Analgesia in Diabetic Mice ALLEN S. LEVINE,*§ JOHN E. MORLEY,*t GEORGE WILCOX,$ DAVID M. BROWN¶ AND BARRY S. HANDWERGERt *Neuroendocrine Research Laboratory, Minneapolis VA Medical Center, Minneapolis, MN 55417 and the Departments of tMedicine, SPharmacology, §Food Science and Nutrition and ~Pediatrics University of Minnesota, Minneapolis and St. Paul, MN Received 18 May 1981 LEVINE, A. S., J. E. MORLEY, G. WILCOX, D. M. BROWN AND B. S. HANDWERGER. Tailpinch behavior and analgesia in diabetic mice. PHYSIOL. BEHAV. 28(1) 39-43, 1982.--Mild tall pinch induced "consummatory" behaviors in mice. The major tail pinch behavior appeared to be chewing with food ingestion occurring possibly as an epiphenome- non. All tail pinch behaviors were obliterated by the dopamine antagonist haloperidol; and the opiate antagonist, nal- trexone, decreased eating without altering chewing. The combination of dopamine blockade and tail pinch induced jumping behavior in mice. Diabetic mice showed increased tail flick latencies to radiant heat and to the induction of tail pinch behaviors, displaying these behaviors less commonly than their homozygote and heterozygote littermate controls. Stress-induced eating Dopamine Appetite Analgesia Diabetes Opiates Naltrexone Diabetic mouse STRESS is well recognized as being capable of precipitating eating in a variety of animals (reviewed in [2]). Several mod- els have been used to study stress induced eating in labora- tory animals. Non-specific stresses which induce eating in- clude acoustic stiumli [7], handling [7], social isolation [22], electrical shock [23, 24, 26] and electrical stimulation of the brain [3,27]. A very well characterized model of stress in- duced eating is mild tail pinch in rats [2, 3, 4, 17, 18, 19]. Mild (non-painful) tail pinch has been shown by Antelman and his colleagues to induce feeding, gnawing and licking in rats [2,4]. This model has been shown to be dopamine dependent [4] and to involve activation of an endogenous opiate system [13,15]. Although most studies have concentrated on the feeding related behaviors following tail pinch, some studies have shown that tail pinch behavior is dependent on the goal objects available in the environment. Thus chewing behavior predominates if wood chips replace the food [10] and tail pinch has been demonstrated to induce copulation in the presence of receptive females [2] and to potentiate maternal behavior in the presence of pups [25]. Also tail pinch has been reported to induce sand digging in rats [28]. It has been suggested that tail pinch represents an eliciting stimulus, which simply activates the organism. This activation enhances its responsiveness to external, food-related stim- uli, which direct behavior towards eating [9]. The studies reported here document the induction of con- summatory behaviors in mice by tail pinch, showing that these behaviors are not species specific. On-going studies in our laboratory had demonstrated different analgesic thresholds in diabetic mice compared to their non-diabetic littermate controls. As we have previously demonstrated that a local anesthetic ring block at the base of the rat's tail abolishes tail pinch behaviors [10] suggesting dependence on nociception for tail-pinch behavior, we felt it would be il- luminating to study tail pinch behavior in a group of mice with different analgesic thresholds, viz. diabetic mice. METHOD For the studies described here we used 54 diabetic mice (db/db) (24 males and 30 females) of the C57BL/ks(db/db) strain and their heterozygote (db/m) (20 males and 25 females) and homozygote (m/m) (19 males and 18 females) controls. All animals were housed in a light controlled room (lights on 0700-1800 hr) with free access to Purina chow and water ad lib. All experiments were carried out between 1300-1700 hr. Animals were between two to three months of age at the time of testing. Blood for glucose levels was obtained by retro-orbital puncture and glucose was measured using a glu- cose analyzer (Beckman: Fullerton, CA). We also docu- mented the daily food intake over a 14 day period. We used the tail pinch method as originally described by Antelman [2,4] for rats and modified by us [17]. Tail pinch was induced with a plastic hemostat (MacBick Co., Murray Hill, NJ) which gives greater control of the range of pressures that can be exerted compared to a surgical hemostat. Behavioral test- ing was carried out in a 22x 17 cm plastic box, unfamiliar to the animal, containing a single pellet of Purina chow (3-6 g). In all animals in whom tail pinch behavior could be induced, induction occurred before the onset of pain as indicated by Squealing. Food ingestion was quantitated by carefully weighing the pellet and spillage before and after the experi- mental period. The tail pinch was continued for 120 seconds after the induction of tail pinch behavior. Analgesia was quantitated by using the tail flick method 39