PII S0031-9384(97)00351-X Participation of the Medial and Anterior Hypothalamus in the Modulation of Tonic Immobility in Guinea Pigs LETICIA DE OLIVEIRA, ANETTE HOFFMANN AND LEDA MENESCAL-DE-OLIVEIRA 1 Department of Physiology, Faculty of Medicine of Ribeira ˜o Preto, University of Sa ˜o Paulo, 14049-900 Ribeira ˜o Preto, SP, Brazil Received 7 February 1997; Accepted 29 May 1997 OLIVEIRA, I., A. HOFFMANN AND L. MENESCAL-DE-OLIVEIRA. Participation of the medial and anterior hypothalamus in the modulation of tonic immobility in guinea pigs. PHYSIOL. BEHAV. 62(5) 1171–1178, 1997.—Tonic immobility (TI) is an inhibitory behavioral response during which the animal presents profound physical inactivity and a relative lack of response to the environment. This response is induced in the laboratory by postural inversion of the animal and brief postural contention of its movements. In nature, the response occurs when there is physical contact between prey and predator. In this case, the physical inactivity of the prey may prevent the continuation of the attack. The neural substrate of this response is not well known and the objective of the present study was to investigate the effect of cholinergic stimulation of hypothalamic regions on TI modulation in guinea pigs (Cavia porcellus). Microinjection of carbachol (1.0 g/0.2 L) into the anterior hypothalamus promoted an increase in the duration of TI episodes. Microinjection of carbachol into the ventro- and dorsomedial hypothalamus, however, promoted a reduced duration of TI episodes. Pretreatment with atropine (0.5 g/0.2 L) showed that the action of carbachol is mediated by muscarinic receptors in the anterior and ventromedial hypothalamus but not in the dorsomedial hypothalamus. The results suggest that the hypothalamic regions may play different roles in the organization of defensive behavioral responses such as TI. © 1997 Elsevier Science Inc. Hypothalamus Tonic immobility Defensive behavior Guinea pig Cholinergic system TONIC immobility (TI), also known as reflex immobility, an- imal hypnosis, ‘‘playing dead’’ or fear paralysis, may be de- fined as an inborn response characterized by a state of profound inactivity and a relative lack of responsiveness to the environ- ment. This immobility response can be induced in the labora- tory by postural inversion and manual restraint of movements. TI can be triggered in many vertebrate and invertebrate species and, in some animals, tactile and proprioceptive stimulation is essential for the production of this response (19,32,46). The duration of TI episodes is quite variable, with the animal remaining motionless for seconds or hours according to the species and the environmental conditions (26). According to Gallup (19), TI occurs during prey-predator confrontation and may be triggered by the intense sensation of fear generated in this confrontation. Ratner (46) proposed that TI may be a terminal defense response that occurs when there is physical contact between prey and predator. The perception of the prey as being dead on the part of the predator may increase the chances of survival of the latter since studies have demonstrated that a struggling prey may be necessary if the predator is to continue its attack (65). During a TI episode the animal presents a reduced response to external stimuli. However, studies of the electroencephalographic pattern of toads (27,28) and chickens (21) and of evoked potentials in rabbits (32) have indicated a state characterized by alert. This evidence suggests that during TI the animal may be monitoring the environment, possibly waiting for a good opportunity for escape. Many studies have been conducted to clarify the neural sub- strate of this response. Pavlov (45) postulated that animal hypnosis was triggered by the inhibition of cortical cells that might exert an inhibitory tonic effect on the subcortical structures involved in this behavior. Indeed, McGraw and Klemm (39) reported that decor- ticated rats become more susceptible and present long TI episodes. Furthermore, Svorad (64) reported that young rats with less de- veloped neocortical influences are more susceptible to TI than adult rats. These results support the theory of cortical inhibition according to which tonic cortical influences inhibit the expression of affective behaviors. Furthermore, this hypothesis agrees with the observation that phylogenetically more advanced species, i.e., species with greater neocortex development, are less susceptible to TI responses. Klemm (32) suggested the possibility of a diffuse limbic and thalamic inhibition of the neocortex that may indirectly facilitate TI induction by the disinhibition of a hypothetical center in the brain stem that may be controlling this response. This theory proposes the association of affective components such as fear and 1 Requests for reprints should be addressed to Leda Menescal-de-Oliveira. E-mail: 1mdolive@fmrp.usp.br Physiology & Behavior, Vol. 62, No. 5, pp. 1171–1178, 1997 © 1997 Elsevier Science Inc. All rights reserved. Printed in the U.S.A. 0031-9384/97 $17.00 + .00 1171