Toxicology Letters, 64l65 (1992) 231-237 0 1992 Elsevier Science Publishers B.V., All rights reserved 03784274/%X@ 5.00
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Developmental aspects of neurobehavioural toxicity G. Bignamia, G. Laviola”, E. Allevaa, R. Cagianob, C. Lacombab and V. Cuomob ‘Laboratory ofPathophysiology, Istituto Superiore di Sanitci, Roma, and bInstitute of Pharmacology, University of Bari, Bari (Italy)
Key words: Prenatal benzodiazepines; Prenatal haloperidol; Behavioural development; Ultrasonic vocalizations; Parental care; Maternal aggression
SUMMARY Previous work on the developmental aspects of neurobehavioural toxicity in rats and mice has shown the reliability of a variety of procedures aimed at assessing changes that may have widespread functional consequences, for example: (i) modified Fox batteries to study the maturation of various reflexes and responses after birth, (ii) activity/habituation and analgesia tests with age-specific profiles of reactivity to selected drug challenges, and (iii) simple learning tasks such as active and passive avoidance 111.We will now summarize more recent work on other portions of the behavioural repertoire which deserve to be thoroughly assessed in “higher-tier” studies.
CHANGES IN SOCIAL AND REPRODUCTIVE BEHAVIOURS
Ultrasonic vocalization in ratpups Ultrasonic emissions by rat pups are considered to be distress calls and indicators of emotionality level [Z]. Figure 1 shows that, in the Bari laboratory, the administration of diazepam (0.1 or 1 mg/kg s.c.) over gestation days 14420 modified the postnatal ultrasonic vocalization pattern 131. While these data strengthen the notion that the benzodiazepine (BDZ)GABA receptor complex plays a role in the physiologic mediation of ultrasonic emissions [Zl, their biological significance remains to be explored. Some preliminary unpublished data show that the decrease in the rate of calling elicited by a diazepam challenge (0.25 mg/kg s.c.) was significantly Correspondence to: G. Bignami, Laboratory of Pathophysiology, Istituto Superiore di SanitB, V. le Regina Elena 299,00161 Rome, Italy.
232
bi120v; +I u looi $ 80-
=
c
. ‘\q Controls DZP 0.1 5 10 15 5 10 15 5 days of age
10
15
Fig. 1. Duration of ultrasonic calls in rat pups exposed prenatally to diazepam (0.1 or 1 mg/kg; see text). *P
231
Developmental aspects of neurobehavioural toxicity G. Bignamia, G. Laviola”, E. Allevaa, R. Cagianob, C. Lacombab and V. Cuomob ‘Laboratory ofPathophysiology, Istituto Superiore di Sanitci, Roma, and bInstitute of Pharmacology, University of Bari, Bari (Italy)
Key words: Prenatal benzodiazepines; Prenatal haloperidol; Behavioural development; Ultrasonic vocalizations; Parental care; Maternal aggression
SUMMARY Previous work on the developmental aspects of neurobehavioural toxicity in rats and mice has shown the reliability of a variety of procedures aimed at assessing changes that may have widespread functional consequences, for example: (i) modified Fox batteries to study the maturation of various reflexes and responses after birth, (ii) activity/habituation and analgesia tests with age-specific profiles of reactivity to selected drug challenges, and (iii) simple learning tasks such as active and passive avoidance 111.We will now summarize more recent work on other portions of the behavioural repertoire which deserve to be thoroughly assessed in “higher-tier” studies.
CHANGES IN SOCIAL AND REPRODUCTIVE BEHAVIOURS
Ultrasonic vocalization in ratpups Ultrasonic emissions by rat pups are considered to be distress calls and indicators of emotionality level [Z]. Figure 1 shows that, in the Bari laboratory, the administration of diazepam (0.1 or 1 mg/kg s.c.) over gestation days 14420 modified the postnatal ultrasonic vocalization pattern 131. While these data strengthen the notion that the benzodiazepine (BDZ)GABA receptor complex plays a role in the physiologic mediation of ultrasonic emissions [Zl, their biological significance remains to be explored. Some preliminary unpublished data show that the decrease in the rate of calling elicited by a diazepam challenge (0.25 mg/kg s.c.) was significantly Correspondence to: G. Bignami, Laboratory of Pathophysiology, Istituto Superiore di SanitB, V. le Regina Elena 299,00161 Rome, Italy.
232
bi120v; +I u looi $ 80-
=
c
. ‘\q Controls DZP 0.1 5 10 15 5 10 15 5 days of age
10
15
Fig. 1. Duration of ultrasonic calls in rat pups exposed prenatally to diazepam (0.1 or 1 mg/kg; see text). *P
