European Journal of PharmacologY, 121 (1986) 189-- 198 189 Elsevier MOTOR EFFECTS OF CALCITONIN ADMINISTERED INTRACEREBROVENTRICULARLY IN THE RAT MICHAEL J. TWERY l, BRIAN KIRKPATRICK 2.3, ELIZABETH C. CRITCHER 3. MARK H. I,EWIS 3 RICHARD B. MAILMAN 1,2,3and CARY W. COOPER 4.. Departments of / PharmacoloKv. " Psychiatry and ~ Biological Sciences Research Center. Unit,er~'ityof North Carolina School of Medicine, Chapel Itill. NC 27514 and 4 Department of Pharmacology and Toxicology. Unit'ersity of Texas Medical Branch. Gah'eston, TX. U.S.A. Received 2 October 1985, accepted 12 November 1985 M.J. TWERY, B. KIRKPATRICK, E.C. CR1TCHER, M.H. LEWIS. R.B. MAILMAN and C.W. COOPER, Motor effects of calcitonin administered intracerebrot:entricularl.v in the rat. European J. Pharmacol. 121 (1986) 189-198. In rats treated with salmon calcitonin (CT) administered intracerebroventricularly (i.c.v., 85 or 8.5 pmol), spasmodic body movements, bopping and tail jerks, collectively termed dyskinesia, appeared within 1 h of administra- tion and persisted for at least 24 h. In addition, spontaneous grooming, rearing and locomotion occurred less often in CT-treated rats than in vehicle-injected animals, while the incidence of both sniffing and nose poking remained essentially unchanged. The CT failed to displace either [3 H]dopamine or [3 H]spiperone from striatal membranes, and the behavioral effects were not blocked by haloperidol or SCH 23390, suggesting that the peptide did not directly affect dopamine receptors. The dyskinesia was not blocked by scopolamine, atropine, muscimol, diazepam or ketanserin. These data are consistent with the hypothesis that a compound with recognition characteristics similar to those of salmon CT may function as a neurotransmitter-modulator in the central nervous system. Calcitonin Behavior Motor function Dopamine Binding Dyskinesia I. Introduction Calcitonin (CT) is a peptide hormone synthe- sized by C-cells in the thyroid gland of mammals and the ultimobranchial gland of lower vertebrates. Embryologically, C-cells are thought to be derived from neuroectodermal tissue (Pearse et al., 1972). The hormone contributes to calcium homeostasis by controlling the efflux of calcium from skeletal sites, and. in coordination with vitamin D and parathyroid hormone, influences the concentration of serum calcium (Munson, 1976). In rats, salmon CT administered intracerebro- ventricular (i.c.v.) leads to decreases in gastric acid secretion (Morley et al., 1981), prolactin release (Pecile et al., 1981; Olgiati et al., 1982), food * To whom all correspondence should be addressed: Depart- ment of Pharmacology and Toxicology. University of Texas Medical Branch, Galveston. TX 77550. U.S.A. consumption (Freed et al., 1979; Perlow et al., 1980), water intake (Twery et al., 1982), response to painful stimuli (Pecile et al., 1975} and the secretion of several pituitary hormones (Pecile et al., 1981: Leicht et al., 1974). In addition, calcitonin is also reported to affect haloperidol-induced catalepsy (Nicoletti et al., 1982) and active avoi- dance behavior (Clementi et al., 1984). It has been suggested that the effects of centrally administered salmon CT mimic the actions of endogenous CT- like substances located within the CNS, and salmon CT-like immunoreactivity (Deftos et al., 1978a,b; Fischer et al., 1981b; Cooper et al., 1980; Fischer et al., 1983), a calcitonin gene-related peptide (CGRP) structurally similar to CT (Amara et al., 1982; Rosenfeld et al., 1983), and high affinity binding sites for salmon CT and CGRP (Fischer et al.. 1981a,b; Henke et al., 1983: Goltzman and Mitchell, 1985) have been reported. Our previous report that calcitonin caused a 0014-2999/86/$03.50 ~: 1986 Elsevier .Science Publishers B.V.