Acoustic startle induced ultrasonic vocalization in the rat: a novel animal model of anxiety?

Ultrasonic vocalization was induced by either high intensity acoustic stimuli or by electric footshock in the rat. High intensity acoustic stimuli elicit a startle response, while electric footshocks provoke an immediate withdrawal of the feet often accompanied by a pain reaction. Flunitrazepam (0.5 mg/kg), diazepam (5 mg/kg), and ipsapirone (5 mg/kg) reduced the vocalization induced by both averse stimuli. Maprotiline (10-25 mg/kg) enhanced the vocalization. FG 7142 (10 mg/kg) had no effect. The acoustic startle-induced vocalization paradigm like the electric footshock-induced vocalization paradigm may provide a simple and reliable tool in the study of anxiety. The advantage of an acoustic pulse as the averse stimulus is discussed.

Acoustic signaling in the black rat (Rattus rattus).

This study surveyed the vocalization repertoire of descendants of wild-trapped Rattus rattus. Sound recordings synchronized with behavioral observations were conducted in an animal colony living undisturbed under seminatural conditions. Analyses of sound recordings revealed 10 distinct acoustic signals, 5 of which were in the ultrasonic frequency range. The time course and the frequency pattern of the analyzed sounds were similar to those described for R. norvegicus, and they occurred in comparable situations. A species-specific difference may be the intensity of the emitted sounds. The possible communicative function of the acoustic signals is discussed.

Startle-inducing acoustic stimuli evoke ultrasonic vocalization in the rat.

The present study demonstrates that acoustic stimuli which induce a startle response (ASR) also evoke ultrasonic vocalization in the rat. Sound recordings were done on three consecutive days of testing during sessions of 20 acoustic stimuli each and on the following day for three minutes following 5 acoustic stimuli (nonstimulus condition). Startle-inducing stimuli evoked continuous ultrasonic calling which was maintained throughout testing. Immediately following each acoustic stimulus, however, vocalization was interrupted by a period of silence (gap). The mean duration of sounds was reduced and the interpulse interval tended to increase during acoustic stimulation as compared to the nonstimulus condition. It is concluded that startle-eliciting stimuli induce a state of fear in the rat and that the acoustic-startle-elicited ultrasonic vocalization may provide a novel model in the study of anxiety.

The interaction of central oxytocin and cholecystokinin regulates grooming behavior in the rat.

Oxytocin (OXY) and cholecystokinin (CCK) coexisting in neurons of the hypothalamic paraventricular nucleus (PVN) induce grooming behavior when microinjected into the ventral tegmentum. The present study sought to investigate two other putative terminal fields of this peptide-peptide coexistence, the lateral hypothalamus (LH) and the medial preoptic area (MPOA), and to determine the functional interaction between OXY and CCK. Microinjection of OXY and CCK alone or in combination into the LH but not into the MPOA induced grooming. Both peptides seem to be equally critical for the induction of grooming; they may interact on a common substrate by suppressing each other's effect.

Ventral tegmental oxytocin induces grooming.

Bilateral microinjection of oxytocin (OXY) into the ventral tegmental area (VTA) of rat brain produced a significant increase in grooming behaviors at doses from 100 pg to 400 ng. Sites in the caudal region of the VTA were sensitive to lower doses of OXY than sites in the rostral region of the VTA. The time course of action of OXY in the grooming paradigm indicated onset beginning immediately after injection, and termination at 60-75 minutes after injection. Comparison of OXY-induced grooming in male, female, and ovariectomized, estrogen-treated female rats showed no differences in potency for OXY among these groups, suggesting that the grooming effects of OXY are not regulated by sex steroids. Analysis of locomotor activity in rats microinjected with OXY 200 ng bilaterally into the caudal VTA revealed that OXY had no effect on ambulatory locomotion, suggesting that this peptide may activate neurons within the VTA which mediate grooming but not locomotion. The OXY receptor antagonist, [Pen1, pMePhe2, Thr4, Orn8]-OT, blocked OXY-induced grooming when both were simultaneously microinjected into the VTA. The dopamine D-2 receptor antagonist, haloperidol, and the D-1 receptor antagonist, SCH 23390, when microinjected into the VTA five minutes before microinjection of OXY into the VTA, did not block OXY-induced grooming, suggesting that OXY is not working through a dopamine autoreceptor on the VTA neurons. Systemic pretreatment with haloperidol and SCH 23390 effectively blocked grooming induced by OXY in the VTA, suggesting that OXY is directly stimulating OXY receptors on VTA neurons to release dopamine at postsynaptic sites regulating grooming behaviors.

Oxytocin and cholecystokinin induce grooming behavior in the ventral tegmentum of the rat.

Oxytocin (OXY) and cholecystokinin (CCK) coexist in neurons of the supraoptic nucleus and the paraventricular nucleus of the hypothalamus of the rat (Cell Tissue Res., 221 (1981) 227-231). Behavioral analysis of one possible terminal field of the OXY-CCK coexistence, the caudal region of the mesencephalic ventral tegmentum, was undertaken to investigate the functional significance of this coexistence. Both OXY and CCK were found to induce grooming behaviors when microinjected into the ventral tegmental area (VTA) of awake rats. Combinations of one low and one higher dose of OXY and CCK yielded grooming scores which were not significantly different from grooming scores induced by each peptide alone. In this case of putative coexistence of two peptides without a 'classical' neurotransmitter, each peptide appears to have a behavioral function, and the interaction between the two peptides may be competitive.

Potency of CR 1409, a new proglumide analog, on cholecystokinin-mediated behaviors and receptor binding.

Behavioral and receptor binding techniques were employed to evaluate the potency of CR 1409, a new analog of proglumide, as a cholecystokinin antagonist. CR 1409, at doses of 1 mg/kg i.p. in mice, effectively blocked the inhibition of feeding and exploratory behaviors induced by cholecystokinin. In rats, CR 1409 alone, at doses of 1 and 10 mg/kg, did not affect feeding or exploratory behaviors, but at 25 mg/kg alone, CR 1409 reduced food intake and exploratory behaviors, suggesting a mixed agonist-antagonist profile. On these several behavorial parameters, CR 1409 antagonized peripherally administered cholecystokinin with 10-1000 times greater potency than that reported for proglumide (Crawley et al., J. Pharmac. Exp. Ther.236, 320-330, 1986). In binding to pancreatic cholecystokinin membranes, CR 1409 was more than 100,000-times more potent than that reported for proglumide (Rovati, Scand. J. Gastroenterol.11, 113-118, 1976). CR 1409 inhabited binding of 125-I-cholecystokinin octapeptide in mouse parcreatic and brain membranes with IC(50) values of 13.7 nM and 2.6 ?M, respectively, demonstrating its selectivity for peripheral-type CCK receptors.