Agmatine reduces ultrasonic vocalization deficits in female rat pups exposed neonatally to ethanol

Abstract

Rat pups, in isolation, produce ultrasonic vocalizations (USVs). These USVs have been used as a diagnostic tool for developmental toxicity. We have shown that neonatal ethanol (ETOH) exposure produces deficits in this behavior. The current study was designed to examine whether agmatine (AG), which binds to imidazoline receptors and modulates n-methyl-d-aspartate receptors (NMDAR), could reduce these deficits. In addition, this study examined critical periods for ETOH's effects on USVs by administering ETOH during either the 1 st or 2 nd postnatal week. Neonatal rats received intragastric intubations of either ETOH (6g/kg/day), ETOH and AG (6g/kg/day and 20 mg/ kg/day), AG (20mg/kg/day), or maltose on postnatal days (PND) 1-7 or 8-14. A non-intubated control was also included. Subjects were tested on PND 15. Neonatal ETOH exposure significantly increased the latency to vocalize for females and reduced the rate of USVs in both males and females exposed to ETOH on PND 1-7. Agmatine reduced these deficits, in female but not male pups. Subjects exposed to ETOH on PND 8-14 showed no evidence of abnormal USVs. These findings suggest that there may be gender differences in response to AG following neonatal ETOH exposure and also provide further support that the first neonatal week is a particularly sensitive time for the developmentally toxic effects of ETOH in rodents.

Conditioned breathing depression during neonatal life as a function of associating ethanol odor and the drug's intoxicating effects

“…High ethanol doses (e.g., 6 g/kg/day) administered during the first postnatal week in the rat consistently decrease neonatal USVs during social isolation; an effect that has been related with alterations in structures of the limbic system involved in emotional processing (e.g., Barron & Gilbertson, ; Barron, Segar, Yahr, Baseheart, & Willford, ). Recent experimental evidence shows that this phenomenon is more pronounced in female pups as has been the case in the present study (Wellmann, Lewis, & Barron, ). Although different hypotheses have been proposed to explain this dimorphism, the complexity of the neurobiological substrates of ultrasonic emissions still does not allow a valid explanation (Wellmann et al, ).…”

Docosahexaenoic acid partially ameliorates deficits in social behavior and ultrasonic vocalizations caused by prenatal ethanol exposure

“…The increased latency can also be seen after neonatal ethanol exposure alone [87, 88]. Typically, these calls are thought to be important for maternal retrieval (e.g.…”

Effects of chronic social stress during lactation on maternal behavior and growth in rats

“…The lack of an effect of CSS on maternal care at day 16 may be due to a compensatory increase in nursing and grooming in the affected dams, possibly stimulated by increased pup vocalizations (Wellmann et al 2010). Another potential explanation is that the maternal behavior testing paradigm was not sensitive enough to detect behavioral differences that would have been apparent through long-term daily observations of undisturbed dams.…”