Pharmacology Biochemistry & Behavior, Vol. 40, pp. 163-168. ©Pergamon Press plc, 1991. Printed in the U.S.A. 0091-3057/91 $3.00 + ,00 Effect of Capsaicin Neonatal Treatment on the Salt Intake of the Adult Rat MAURIZIO MASSI,* CARLO POLIDORI,* MARINA PERFUMI,* ROBERTO CICCOCIOPPO,* GIUSEPPE DE CARO,* CARLA BACCIARELLIt AND STEFANO MANZINIt *Institute of Pharmacology, University of Camerino, Via Scalzino 5, 62032 Camerino (MC), Italy and "PDepartment of Pharmacology, Malesci Pharmaceuticals, Via Porpora 22, 50144 Firenze, Italy Received 22 Janual'y 1991 MASSI, M., C. POLIDORI, M. PERFUMI, R. CICCOCIOPPO, G. DE CARO, C. BACCIARELLI AND S. MANZINI. Effect of capsaicin neonatal treatment on the salt intake of the adult rat. PHARMACOL BIOCHEM BEHAV 40(1) 163-168, 1991.- The present study investigated the involvement of capsaicin-sensitive sensory neurons on salt intake control in the rat, following capsaicin neonatal treatment. Capsaicin did not affect salt appetite induced by intramuscular injection of deoxycortieosterone enan- tate, or by intracranial injection of renin. Moreover, it did not alter salt preference of rats given access to a variety of NaC1 concentrations, or the need-free salt intake of multidepleted male rats. On the other hand, in response to furosemide-induced sodium depletion, the salt intake of capsaicin-treated rats was lower than that of controls. However, furosemide-induced Na + excretion of capsalcin-treated rats proved to be lower than that of controls, thus suggesting that difference in salt intake might be secondary to lower sensitivity of capsalcin-treated rats to the natriuretic action of furosemide. Salt intake is known to be influ- enced by sensory information from the oral cavity, from the liver and from the intravascular compartment. The absence of effect of capsalcin neonatal treatment suggests that sensory fibers relevant to salt intake control may not be capsalcin sensitive. On the other hand, our findings indicate that capsalcin treatment alters the renal response to furosemide and stimulate further studies on the effects of capsalcin on renal function. Capsaicin Salt appetite Furosemide Sodium excretion Urine volume CAPSAICIN, the pungent constituent of some red peppers of the genus Capsicum, is commonly used as a neurotoxin to elucidate the function of primary sensory afferent neurons (3). Capsaicin stimulates the peripheral endings of certain primary afferents, resulting in sensory impulse generation and local transmitter re- lease (16, 28, 29). Shortly after its stimulating action, the sen- sory fibers become inexcitable by capsaicin itself and, following administration of high concentrations of the drug, also by other chemical and physical stimuli. This phenomenon, the so-called capsaicin "desensitization," involves blockade of both sensory and efferent function without degenerative changes in nerve fi- bers, and at high doses it is accompanied (hours-days after cap- salcin challenge) by depletion of neuropeptides, such as substance P, neurokinin A and calcitonin gene-related peptide, from pe- ripheral stores of sensory neurons (16, 17, 28, 29). Finally, neonatal capsaicin treatment in the rat is known to produce de- generation of neuropeptides-containing capsaicin-sensitive sen- sory nerves (25). In relation to our interest in the study of the neural mecha- nisms controlling salt appetite, we thought it interesting to eval- uate the effect of neonatal capsaicin treatment on the control of salt intake in the adult rat. Three main reasons have stimulated the present study: a) It is well established that seOsory informa- tion from the periphery (oral cavity, liver, intravaseular compart- men0 contributes to the arousal and to the saliation of the appetite, but it is presently unknown whether it i S mediated by capsaicin-sensitive sensory neurons (2, 4, 5, 11, 12, 14, 30, 32); b) A recent study has shown that capsalcin treatment in neonatal rats enhances the intensity of deoxycorticosterone (DOC)/salt-in- duced hypertension. Since this experimental model of hyperten- sion is heavily dependent on salt intake, the question arises whether the enhanced hypertension of capsaicin-treated rats might be secondary to capsaicin influence on salt intake control (18); and c) Our previous studies have shown that tachykinin peptides, which are present in capsalcin-sensitive sensory neurons, exert a potent antinatriorexic action acting in the forebrain of the rat (19-23), but it is still unknown whether they might contribute to salt intake control also as sensory neurotransmitters in peripheral sensory nerves. METHOD Anima/s Pregnant Wistar-Nossan female rats were housed in the ani- mal care unit at least one week before parturition. On days 1-2 of life, neonatal rats received in the dorsal thoracic region cap- salcin (50 mg/kg b.wt., subcutaneously; SC) or the vehicle (10% ethanol, 10% Tween 80 and 80% isotonic saline). The injection volume was 3 ixl/g. After 4 weeks, male and female rats were divided and housed 4-5 to a cage with food and water ad lib. Validity of capsalcin treatment was checked by evaluating the loss of the wiping reflex to capsaicin (0.01%) instillation into the eye. Experiments were performed in 2--4-month-old rats. Adult rats were individually housed in a temperature-con- 163