Ontogeny of tactile, vocal and kinship dynamics in rat pup huddling.

Effects of prenatal exposure to valproic acid or poly(I:C) on ultrasonic vocalizations in rat pups: The role of social cues

Ultrasonic vocalizations in rat pups: effects of serotonergic ligands

P.1.026 - Prolactin and TSH responses to TRH and to ECT in pre- and post-menopausal women with major depression

ObjectiveThe goal of this study was to identify changes in quantitative and qualitative aspects of neonatal ultrasonic vocalizations USVs in neuron‐subset specific (NS‐Pten) knockout males and females when compared with wild‐type male and female mice.BackgroundOne signaling cascade that plays a crucial role in the development of an autistic‐like phenotype is the PI3K/Akt/mTOR pathway. Mouse models that illustrate this connection include Fmr1, Tsc1, and NS‐Pten‐deficient mice. While numerous studies have investigated ultrasonic vocalizations in Fmr1 knockout and Tsc1 heterogenous mice, none have investigated USVs in NS‐Pten knockout mice using a full spectrum recording system.MethodsWe recorded ultrasonic vocalizations from NS‐Pten wild‐type and knockout male and female mice on postnatal days 8 and 11. On these days, we measured the number and quality of calls emitted from pups when they were removed from their mothers.ResultsWe found that knockout pups emitted fewer vocalizations for both sexes (p < .05). Knockout males had calls of a shorter duration and lower peak amplitude on day 8, while showing a shorter duration, lower peak amplitude, and higher peak and fundamental frequency on day 11 (p < .001). Knockout females vocalized at a lower peak amplitude and fundamental frequency, and a higher peak frequency on day 8, while showing a shorter duration and a higher peak and fundamental frequency on day 11 (p < .001). Spectrographic analyses also revealed significant differences in call type for both genotypes and sexes (p < .05).ConclusionsThese findings demonstrate that deletion of NS‐Pten results in significant decreases in vocalizations across both sexes. Additionally, our findings indicate that the aberrant vocalizations and increased call duration seen in other mTOR models are also present in NS‐Pten knockout mice. Our study provides evidence of a connection between hyperactive mTOR signaling and neonatal ultrasonic vocalizations.

Acoustic alterations of ultrasonic vocalization in rat pups induced by perinatal hypothyroidism

Caretaking stability in the early life environment supports neurobehavioral development, while instability and neglect constitute adverse environments that can alter maturational processes. Research in humans suggests that different types of early life adversity (ELA) can have differential effects on caretaker relationships and later cognitive and social development; however, identifying mechanistic underpinnings will require animal models with translational validity. Two common rodent models, maternal separation (MS) and limited bedding (LB), influence the mother-infant relationship during a critical window of development. We hypothesized that these paradigms may affect the development of communication strategies on the part of the pup. Ultrasonic vocalizations (USVs) are a care-eliciting mechanism and ethologically relevant response to stressors in the rat pup. USV emission rates and acoustic parameters change throughout early development, presenting the opportunity to define developmental milestones in USVs that would reflect neurobehavioral aberrations if disrupted. This study investigated the effects of MS or LB on the dam-pup relationship by quantifying pup USVs, maternal behavior, and the relationship between the two. First, we used a generalized additive model approach to establish typical developmental trajectories of USV acoustic properties and determine windows of change in MS or LB rearing. Additionally, we quantified maternal behaviors and the predictability of maternal care sequences using an entropy rate calculation. MS and LB each shifted the developmental trajectories of USV acoustic parameters and call types in a sex-specific manner. MS more often impacted male USVs, while LB impacted female USVs. MS dams spent more time passive nursing, and LB dams spent more time on the nest. The predictability of maternal care was associated with the rate of USV emissions exclusively in females. Taken together, findings demonstrate sex- and model-specific effects of rearing environments on a novel developmental trajectory involving the mother-infant relationship, facilitating the translation of animal ELA paradigms to assess later-life consequences.

Effect of lithium-pilocarpine-induced status epilepticus on ultrasonic vocalizations in the infant rat pup

Ultrasonic vocalizations (USVs) are a major means of communication in rats, and can be emitted by rat pups, as well as by young and adult rats. Several lines of evidence indicate that the emission of USVs has behavioral significance, and may reflect either euphoric (positive) or dysphoric (negative) emotional states in the rat [1, 2]. This renders rat USVs an appealing behavioral parameter to be considered in studies of emotion, motivation, and reward. Moreover, rat USVs have recently begun to be investigated in pharmacological studies associated with effects of drugs of abuse, in the light of previous findings showing that certain addictive drugs can influence the emission of USVs by rats [3-5]. Finally, evidence also exists that altered emission of USVs by rats may be linked to either neurological abnormalities [6, 7], or to genotypes/phenotypes that may exhibit behaviors reminiscent of certain neuropsychiatric conditions [8, 9]. Based on these considerations, rat USVs have recently attracted attention as a complementary, non invasive, behavioral measure in neuropharmacological studies. The aim of this special issue is to present an updated overview of the behavioral significance of rat USVs and to discuss the relevance of these USVs to neuropharmacological studies. Behavioral significance of rat USVs is presented in the review by Brudzynski [10], which contains an exhaustive overview of the behavioral and pharmacological studies of basic emotional states signaled by USVs, and a thorough discussion on the relevance of rat USVs as experimental tools in studies of emotional states. This paper also includes information about neurochemical bases of these states expressed by emission of relevant USVs. The review by Simola [11] discusses possible use of rat USVs measurements in neuropharmacological and drug discovery studies, by reviewing the current evidence that shows how rat USVs may be a suited tool for investigating properties of certain classes of agents (e.g., anxyolitics, antidepressants, drugs of abuse) and as correlates of behaviors reminiscent of psychiatric syndromes (e.g., anxiety, autism, depression). More specific aspects of rat USVs are covered by the other reviews in the issue. Barker et al., [12] review the current evidence of using rat USVs to study the affective components of drug abuse and drug withdrawal. This paper includes critical discussion on how rat USVs may complement the current experimental paradigms of drug abuse and reveal the affective processes that may promote drug taking and/or relapse. The review by Johnson et al., [13] presents evidence that changes in the emission of rat USVs and in their acoustic features occur in models of neurodegenerative disorders, which suggests that the study of USVs could represent a new complementary behavioral measure in investigations of neuronal death. Finally, Rippberger et al., [14] provide an updated overview of the neurochemical mechanisms and experimental conditions that promote the emission of rat USVs in response to amphetamine, a prototype drug able to stimulate reward-related USVs in the rat. This paper also suggests that emission of these USVs may have some relevance to the experimental study of mania. By gathering high-quality and updated reviews, this special issue should contribute to an increased awareness of the scientific community as to the significance and use of rat USVs as a new complementary behavioral measure in neuropharmacology.

Cannabinoid modulation of rat pup ultrasonic vocalizations

Effects of decabromodiphenyl ether (BDE-209) on ultrasonic vocalizations emitted by rat pups during isolation

Involvement of the strychnine-sensitive glycine receptor in the anxiolytic effects of GlyT1 inhibitors on maternal separation-induced ultrasonic vocalization in rat pups

The role of cholecystokinin (CCK) in reducing separation-induced ultrasonic vocalization (USV) was examined by peripheral administration (of the selective CCK(A) receptor antagonist devazepide to 10-11-day-old rats. Pups placed alone for 2 min emitted a mean of 55.1 USV/min. When placed on a paper towel wet with warm, sweet milk, USV rate decreased to 23.2/min for the following 8 min. Devazepide (150-600 microg/kg IP) prevented this USV reduction, but did not increase feeding. In contrast, USV reduction produced by contact with the anesthetized dam was not affected by devazepide. Similarly, the opiate antagonist naltrexone (0.5 and 1.0 mg/kg) has been shown to block morphine-induced USV decrease in pups away from the dam, but was ineffective when USV reduction was induced by the presence of the dam (Blass et al., 1990; Carden & Hofer, 1990). The current findings suggest that CCK's role is specific, in that it mediates milk- but not dam-induced quieting of USV. The results, however, are not incompatible with the possibility that CCK and opioids are part of multiple, redundant pathways that mediate the quieting of USV by the dam.

The ontogenetic changes in responsiveness to benzodiazepine receptor ligands on ultrasonic vocalizations in rat pups from the age of day 3 to day 12 were evaluated. Rat pups, while separated from their dam and littermates and placed in a cold environment, emit ultrasonic vocalizations. These ultrasonic calls became attenuated dose-dependently in number and power after administration of the anxiolytic diazepam (0.25-1.0 mg/kg, s.c.), but the inhibitory effect of diazepam at the highest dose was less on day 6 and day 9. Moreover, type 1 benzodiazepine receptor ligands, Ro16-6028 and Ro23-0364 (0.5-2.0 mg/kg, s.c.), also dose-dependently attenuated the ultrasonic vocalizations 30-60 min after injection. The inhibitory effects of these drugs became more pronounced with the increasing age of the pup, and they were equivalent on day 12 to those in adult rats. These results suggest that different ontogenetic changes in development of two subtypes of central benzodiazepine receptors of pups might be related in the psychopharmacological mediation of the ultrasonic vocalization.

Described in this unit is the ultrasonic distress vocalization test in rat pups. This test is a reliable method for detecting anxiolytic properties of test compounds. In this test, ultrasonic vocalizations (30 to 50 kHz) are elicited by separating rat pups of 9 to 11 days of age from their mother and littermates for a brief period of time. The test can be performed under two different stress conditions. Pups are placed in isolation in either a warm (37°C) or cold (18°C) environment for 5 min. The total number and duration of ultrasonic calls emitted by the pups during this period is used as an index of anxiety. Established anxiolytic compounds, including benzodiazepines, serotonin(1A) receptor agonists, and selective serotonin reuptake inhibitors (SSRIs), consistently reduce the number and cumulative duration of these ultrasonic distress vocalizations.

P.3.d.011 In vitro and in vivo characterization of glycine transporter type-1 by two inhibitors, Org-24461 and NFPS