Action of enpiprazole on emotional behavior induced by hypothalamic stimulation in rats and cats

Abstract

Action of enpiprazole on emotional behavior elicited by hypothalamic stimulation in rats and cats was investigated and comparisons were made with effects of diazepam. Two behavioral patterns were elicited by stimulation of the postero-medial part of the hypothalamus in rats: a food-carrying response beginning with exploratory movement and an analogue of fear. Enpiprazole frequently changed the food-carrying response into food-taking response and occasionally analogues of fear into food-carrying and /or food-taking responses. Thresholds for these behaviors were also elevated. Diazepam showed the same effects on the thresholds as enpiprazole, having but little effect on the behavioral patterns. In cats, enpiprazole evelvated the thresholds for affective-defensive responses induced by hypothalamic stimulation in 6 of 8 cases, but lowered them in 2 cases. This suggests that enpiprazple has a 'biphasic effect' in the central nervous system. By contrast,diazepam consistently elevated thresholds. Comparing the action of enpiprazole with that of diazepam it can be presumed that the former is a different type of anxiolytic drug than the latter.

Effects of psychotropic drugs on the rage responses induced by electrical stimulation of the medial hypothalamus in cats.

“…In the present experiment, chlorpromazine and haloperidol did not change the hissing threshold at the dose of 1 mg/kg. This result is consistent with the finding of Murasaki et al (8). They found that haloperidol did not change the threshold for hissing.…”

“…It has been reported that diazepam pro duced marked elevation in the threshold for directed attack induced by electrical stimu lation of the ventromedial hypothalamic nucleus (7,8 From these results, it is concluded that directed attack is inhibited markedly by anti anxiety drugs.…”

Preclinical pharmacology of midazolam.

“…Effect on aggressive rage reaction An emotional aggressive behaviour (rage reaction) can be elicited in unrestrained cats by high frequency electrical stimulation of the hypothalamus (see Glusman (1974) for a detailed review). Diazepam and other benzodiazepines have been reported (Malick, 1970;Murasaki et al, 1976) to elevate the stimulus threshold for eliciting this rage reaction.…”

“…Diazepam and other benzodiazepines have been reported (Malick, 1970;Murasaki et al, 1976) to elevate the stimulus threshold for eliciting this rage reaction.…”

Attenuation of defensive threat and attack in wild rats (Rattus rattus) by benzodiazepines

“…In rodents, benzodiazepines have consistently been found to attenuate defensive reactions induced by a variety of techniques, including conspecific attack (Chance and Silverman 1964;Poole 1973;Miczek 1974;Krsiak 1975;Krsiak et al 1981Krsiak et al , 1984Yoshimura and Ogawa 1984), the presence of a predator (Cameron and Blampied 1980), septal lesions (Schallek et al 1962;Horovitz et al 1963;Stark and Henderson 1966;Beattie et al 1969;Sofia 1969;Goldberg 1970), anterior hypothalamic lesions (Blyther and Marriott 1969), hypothalamic stimulation (Panksepp 1971;Murasaki et al 1976), dorsal PAG stimulation (Graeff et al 1986), apomorphine treatment (Senault 1970) and footshock (Hoffmeister and Wuttke 1969;Sofia 1969;Tedeschi et al 1969;Christmas and Maxwell 1970;Irwin et al 1971 ;Manning and Elsmore 1972;Quenzer et al 1974;Robichaud and Goldberg 1974). Furthermore, and almost by definition, benzodiazepines attenuate aspects of defense elicited by stimuli employed in animal models of anxiety (see Treit 1985 for recent review).…”