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Biomedical subjects

M A Hofer

Publications and source records attributed to M A Hofer.

At least 19 recordsLinked to original sources
PubMed1997

Potentiation and inhibition of ultrasonic vocalization of rat pups: regulation by social cues.

Eight- and 11- to 12-day-old rat pups were tested in isolation and in the presence of an anesthetized adult under cold conditions. Pups of both ages reduced rates of ultrasonic vocalization (USV) when an adult was placed into the test cage, independent of whether the adult was their dam or an unrelated male. However, after removal of the dam, pups greatly increased their rates of USV over their first isolation period and in comparison with control pups. USV rates remained low after removal of the male. The temperature challenges faced by the pups in the two experimental conditions were the same. These phenomena are better explained by a hypothesis that postulates USV rate as being multiply determined, including by social cues, rather than a theory that considers thermal challenge only.

Animals↗
PubMed1996

Development of ultrasonic vocalization responses in genetically heterogeneous National Institute of Health (N:NIH) rats. I. Influence of age, testing experience, and associated factors.

The N:NIH strain of rats was developed by the National Institutes of Health to provide a maximally heterogeneous population as a base for selective breeding (Hansen & Spuhler, 1984). Using the N:NIH strain, this laboratory will selectively breed adult animals that exhibited extremes of high or low ultrasonic vocalization (USV) rates as infants. Because nothing was known about USV in N:NIH rats, we characterized the development of isolation-induced USV in the first generation of this strain born in our laboratory. In a longitudinal/cross-sectional study of pups tested at 3, 10, 15, and 18 days postnatally, N:NIH pups emitted their highest rates of USV at 3-4 days postnatally and calling remained high for 10 days before declining. USV rates were found to be a relatively environmentally stable behavioral trait in that repeated testing did not significantly affect the calling rates of either individuals or litters, and only at 3 days postnatal age did naturally occurring ambient temperature variations (6 degrees C range) significantly affect USV responses. Individual differences in USV responses emerged by 10 days of age that were not simply correlations of body weight or rectal temperature, and pups at that age showed isolation calling rates that were highly predictive of their response levels 5 days later.

Animals↗
PubMed1996

Development of ultrasonic vocalization responses in genetically heterogeneous National Institute of Health (N:NIH) rats. II. Associations among variables and behaviors.

In this study, the first three generations of laboratory-reared, 10-day-old pups of the N:NIH strain were examined for ultrasonic vocalizations (USV) rates in response to 2 min of isolation. The purpose of the study was to determine baseline USV rates in these progenitor (PR1, PR2, PR3) generations prior to selective breeding for high and low rates of USV. In addition, this study aimed to detect sources of variation in USV between and within generations and sexes, and factors associated with USV during isolation across the generations. Data were collected from 532 10 day-old pups in 81 litters. Evaluation by principal component analyses revealed four factors corresponding roughly to constructs indicative of: thermoregulation; maturity and exploratory behavior; distress/anxiety, in which USV consistently appeared; and activity. Different component structures for each sex suggested that USV may represent different dimensions of anxiety for component structures for each sex suggested that USV may represent different dimensions of anxiety for the sexes, with some degree of overlap. Nonetheless, all variables measured during isolation testing accounted for only a small portion of the variance in individual pup USV (less than 9%) at 10 days of age, when the effects of intercorrelations among all variables were taken into account. This suggests that variables currently measured do not represent a comprehensive model for the control of USV.

Animals↗
PubMed1996

Elevated plus-maze behavior in adult offspring of selectively bred rats.

Animals sampled from the third generation (S3) of selective breeding of N:NIH strain rats based on ultrasonic vocalization (USV) rates in infancy (High, Low, and Random lines) were tested as adults on the elevated plus maze, a well-validated test of anxiety. Results showed that the Low line spent a greater percent of time in the open arms of the maze than High and Random (control) line animals, and a lower percent of time exploring from a relatively more protected position. There were no significant sex differences. The present study represents a probe into the processes at work during the early stages of selection for infant USV, and suggests that an adult measure of anxiety may be affected by selection for this infantile behavior.

Animals↗
PubMed1996

Isolation alters striatal met-enkephalin immunoreactivity in rat pups.

Isolated preweanling rats emit ultrasonic vocalizations. Mu- and delta-opioid agonists quiet isolated pups; naltrexone, an opioid receptor blocker, prevents this quieting. A littermate companion is as effective as morphine in quieting vocalizations, and naltrexone also blocks companion quieting. We have now quantified methionine enkephalin (Met-ENK) immunoreactivity in the brains of 10-day-old Wistar rat pups taken directly from the home cage or kept either alone or with a companion for a brief or prolonged period. Met-ENK is an endogenous ligand that binds to the mu- and delta-opioid receptors. Striatal peptide levels were higher when pups were with a companion than when they were kept alone; the peptide level of pups in the home cage did not differ from either. Comparisons of pups in the brief (5 min) and prolonged (60 min) separation conditions showed significantly higher peptide levels following a brief period out of the nest than at the end of an hour. In hypothalamus, hippocampus, and frontal cortex neither social condition nor duration of separation significantly altered peptide quantity. Larger amounts of Met-ENK in pups provided with a companion could reflect an increase in posttranslational cleavage of the precursor molecule leading to stimulation of receptors that act to diminish USV. Reduced levels following 60 min out of the home cage might reflect depletion of the peptide following an initial release during the period when the pup's vocal response is most vociferous.

Animals↗
PubMed1996

Multiple regulators of ultrasonic vocalization in the infant rat.

This paper reviews our growing understanding of the external environmental and the internal neuroregulatory mechanisms for the infant rat's vocal response to abrupt isolation from nest, littermates and mother. Interactions of the rat pup with specific components of its animate and inanimate environment have been identified and found to exert a tonic regulatory action on the neural systems mediating ultrasonic vocalization (USV). In isolation, withdrawal of these regulators produces an acute outburst of calling. Changes in rate of ultrasonic calling in response to administration of receptor agonist and antagonist agents generally correspond to the effects of those agents on measures of anxiety in adult animals and in human clinical populations, suggesting a conservation of neural substrates for anxiety in evolution and in development. The inhibition of isolation calling in response to predator cues and its potentiation by brief exposure to maternal cues, represent novel forms of regulation with implications for neuroendocrine development and for the neurobiology of early cognitive-emotional processes.

Adult↗
PubMed1996

The isolation and companion comfort responses of 7- and 3-day-old rat pups are modulated by drugs active at the opioid receptor.

Rat pups emit ultrasonic vocalizations (USVs) when isolated in a novel environment. In 10-day-olds, USV has been shown to be reduced by either the administration of 0.125 mg/kg morphine (MOR) or the presence of a littermate; these effects were both reversed by naltrexone (NLX), an opioid receptor blocker. The present study reports that the same dose of MOR produced NLX-antagonized quieting without sedation in 7- and 3-day-old pups; higher doses of MOR decreased USV but produced motor deficits as well. The 0.125 mg/kg dose of MOR is less effective in reducing USV in 3- and 7-day-olds; calling rates declined by no more than 42%, compared with 65% at 10 days of age. The presence of a companion also lowered the USV of 3- and 7-day-olds by a lesser amount (55-57%) than the 67% seen in 10-day-olds or the 90% decline when pups are 2 weeks old. This suggests that age-related changes in the opioid system may be relevant to the increased salience of a social companion that comes with maturity.

Age Factors↗
PubMed1996

Maternal interactions prior to separation potentiate isolation-induced calling in rat pups.

The vocal response rates of 12-13-day-old infant rats to isolation in a bare test box are markedly increased by brief (1-min) periods of contact with an anesthetized dam prior to isolation, without affecting other isolation-induced behaviors. No such potentiation followed brief contact with littermates, novel test conditions, or experimenter handling. Brief contact with the dam was equally effective in the test chamber or home cage and was not further enhanced by repeated contact-separation sequences. Passive contact became ineffective when prolonged to 30 min, and potentiation could not be restored by providing the additional reinforcing events of continuous suckling, periodic oxytocin-induced milk letdown, or bouts of simulated maternal licking. However, when pups engaged in active interaction with an awake dam, potentiation was significantly enhanced following 1-, 10-, and 30-min periods. A working hypothesis is outlined for the adaptive role of potentiation in the development of the rat pup.

Animals↗
PubMed1994

U50,488 increases ultrasonic vocalizations in 3-, 10-, and 18-day-old rat pups in isolation and the home cage.

Separation-induced calling in the young of many species can be modulated by the opioid system. Morphine reduces ultrasonic vocalizations (USVs) produced by isolated rat pups, an effect blocked by naltrexone. Central administration of the mu and delta opiate receptor agonists DAMGO and DPDPE reduce USV; kappa receptor agonist U50,488 increases them. We now find that peripheral U50,488 not only boosted calling rates in isolated 3-, 10-, and 18-day-old rat pups, but also induced calling in pups of these ages tested in the home cage with their littermates, where USVs are seldom heard in nature. U50,488 lowered rectal temperature, although temperature loss and USV were not correlated within drug treatment groups.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗
PubMed1994

Potentiation of isolation-induced vocalization by brief exposure of rat pups to maternal cues.

Since their discovery in 1956, the highest rates of ultrasonic vocalization (USV) have been recorded from infant rats when first isolated in an unfamiliar place. We now report that peak USV rates can be doubled by allowing test pups a brief initial period of contact with their anesthetized dam (1-10 min) in the test chamber before isolating the pup by her removal. Potentiation of the isolation response was specific to the dam, for it failed to occur following initial contact with a group of 4 warm, anesthetized littermates. Control experiments showed that potentiation could not be attributed to thermal contrast, experimenter handling, general behavioral activation, novelty of maternal cues, or nursing deprivation. Furthermore, it did not occur when pups were taken for isolation testing directly from prolonged contact with their anesthetized dam in the home cage. Potentiation may be understood in terms of the communicative role of the pups' call and/or prior learning contingencies within the mother-infant interaction.

Animals↗
PubMed1994

Reduction of rat pup ultrasonic vocalizations by the neuroactive steroid allopregnanolone.

Several of the recently characterized neuroactive steroids have been proposed to have anxiolytic effects in behavioral models when subjects were tested as adults. In this experiment, the effects on infant subjects were examined using the isolation distress model of anxiety. The production of ultrasonic vocalizations in week-old rat pups after maternal separation was assessed after ICV injections of vehicle or allopregnanolone (1.25-5 micrograms), or sham injections. Subjects were also observed for activity and behavioral responses and tested on three measures of sedation. Allopregnanolone caused a dose-dependent decrease in ultrasonic vocalizations, with increasing motor incoordination, ataxia, and turning at the higher doses. Sex differences were not observed for any measure. These results suggest the GABAA receptor binding site for neuroactive steroids is behaviorally active in neonates as well as in adults, and that the anxiolytic effects of the neuroactive steroids at this site may be dissociable from their sedative effects at low doses.

Animals↗
PubMed1994

Hypothermic vocalizations of rat pups (Rattus norvegicus) elicit and direct maternal search behavior.

Emissions of ultrasonic vocalizations (USVs) by rat pups (Rattus norvegicus) during hypothermia have consequences for recovery and warming. We investigated the effects on dam behavior of USVs emitted by 3- to 11-day-old pups during hypothermia at rectal temperatures between 18 and 22 degrees C. Rat dams were tested in a Y maze with the home cage as a start box. Dams were given, in one condition, a choice between a hypothermic pup emitting USVs or a hypothermic, silent (anesthetized) pup and, in the other, a choice between 2 hypothermic, silent pups. Although differing in some acoustic properties from normal isolation calls, USVs emitted by hypothermic pups both elicited maternal search behavior and acted as directional cues for dams, in comparisons with control dams exposed only to silent pups. Thus USVs of pups recovering from extreme hypothermia have communicative as well as physiological significance.

Animals↗
PubMed1994

Early relationships as regulators of infant physiology and behavior.

In recent years, animal research has revealed a network of simple behavioral and biological processes that underlie the psychological constructs we use to define early social relationships. Hidden within the observable interactions of parent and offspring are sensorimotor, thermal and nutrient-based events which have unexpected and widespread regulatory effects on infant behavior and physiology. The complex pattern of responses resulting from early separation in infant rats can be traced to the abrupt withdrawal of a number of discrete, independent regulatory processes which had been acting on individual components of the infant's physiology and behavior. These regulatory processes also appear to mediate long-term shaping effects exerted by early relationships, for example, on the vulnerability of the adult rat to hypertension and stress ulcer. In human development, early regulatory interactions may provide a bridge between biological and psychological processes in the development of our earliest mental representations.

Animals↗
PubMed1993

Ultrasonic vocalization responses of rat pups to acute separation and contact comfort do not depend on maternal thermal cues.

In order to assess the importance of maternal thermal cues in controlling the acute USV responses of rat pups to contact with her body (the contact comfort response) and to separation from her, we drastically altered maternal temperature by inducing severe hypothermia so that maternal rectal and flank temperatures averaged more than 20 degrees C below normal and 10 degrees C below ambient levels during testing. Isolated 12- to 13-day-old pups showed reductions in USV when these cold dams were presented and brisk USV accelerations when the cold dams were removed from the test chamber. These responses closely resembled those of other pups tested with warm (36 degrees C) anesthetized dams. No significant differences were found in pups' USV contact comfort responses to cold and warm dams. For acute separation, prior maternal thermal properties and other factors were found to modulate the relative intensity of the marked USV increase elicited by this event.

Animals↗
PubMed1993

The effects of 24-hr maternal separation and of litter-size reduction on the isolation-distress response of 12-day-old rat pups.

We asked whether the mother-infant interaction acted over time to regulate the ultrasonic vocalization (USV) and activity responses of 12-day-old rat pups to isolation in a novel test area. In a series of four experiments, we found that 24 hr of maternal deprivation did not alter USV isolation responses, but that reduction of litter size to 4 pups from 8 markedly attenuated the USV response and increased weight gain, without effects on activity level. Ambient temperatures during 24-hr maternal separation were varied from 23 degrees to 35 degrees C without effect on subsequent USV responses, but activity levels were markedly reduced in pups separated at the low heat level. Possible mechanisms for maternal regulation of USV responses involving nutrient effects, altered processing of thermal stimuli, and the inhibition of thermogenesis by nutrient deprivation are discussed.

Animals↗
PubMed1993

Afferent control of pressor responses to feeding in young rats.

A series of experiments investigated the eliciting stimuli and physiological systems involved in triggering the blood pressure (BP) response to feeding in the young rat. The studies included 1) tongue cannula (TC) infusions of milk to nipple-attached and unattached pups; 2) TC infusions of saline, sucrose, and water to nipple-attached pups; 3) maternal milk ejections to 3-week-old pups that rarely have stretch responses; 4) gastric cannula infusions of milk to nipple-attached pups; and 5) maternal milk ejections and TC infusions to pups whose mouths were topically anesthetized. The results implicate the contact of fluid with oral and/or lingual surfaces as the critical stimulus primarily responsible for the BP rise. Although nipple attachment appears to be an important precondition for the typical pressor response, the co-occurrence of a behavioral stretch response is not essential.

Afferent Pathways↗