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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
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↗
PubMed1993

Ultrasonic vocalization, laryngeal braking, and thermogenesis in rat pups: a reappraisal.

In these experiments we tested the hypothesis that the respiratory events underlying rat pup ultrasonic vocalization (USV) facilitate brown adipose tissue (BAT) thermogenesis, as proposed by Blumberg and Alberts (1990). Laryngeal denervation or tracheostomy were used to reduce or eliminate laryngeal braking and prevent USV in 9- to 10-day-old pups during recovery from deep hypothermia and during cooling induced by isolation for 1 hr at room temperature. Both forms of devocalization slowed rewarming of hypothermic pups, but neither had any effects on cooling rate or BAT thermogenesis in normothermic pups that were allowed to cool from 35 degrees C to 29 degrees C. Physiological effects of laryngeal braking on thermogenesis appear to be limited to conditions, such as severe hypothermia, in which ventilatory and oxygen transport functions are compromised. The results have implications for understanding the regulation and evolution of USV.

Adipose Tissue, Brown↗
PubMed1993

Ultrasonic vocalizations are elicited from rat pups in the home cage by pentylenetetrazol and U50,488, but not naltrexone.

Although isolated rat pups emit ultrasonic vocalizations (USVs), those kept warm and undisturbed in the home cage with their littermates seldom do. Drugs were administered to 10-day-old pups in the home cage to determine whether pharmacological agents can elicit USV in this familiar environment. Ten-day-old Wistar rats were injected with U50,488, a highly selective kappa opioid agonist; pentylenetetrazol (PTZ), an anxiogenic drug that binds at the GABA-benzodiazepine receptor complex; or naltrexone (NLX), an opiate receptor blocker, and then were returned to their littermates in the home cage. U50,488 increased USV and activity levels, lowered body temperature, and disrupted contact with littermates. PTZ raised activity levels but had a smaller effect on vocalization rates and did not alter temperature or contact with littermates. Behavioral measures and body temperature were unchanged by NLX.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗
PubMed1992

Feeding in infancy: short- and long-term effects on cardiovascular function.

Cardiovascular responses of adult organisms to feeding are well characterized and, in general, are understood as acute adaptations required for processing and distributing nutrients. Research over the past several years has shown that infants also have important cardiovascular responses to nutrient intake and that these are regulated by changes in autonomic activity to the heart and vasculature. Recent studies have provided results that suggest these responses in infancy may make an important contribution to the long-term development of cardiovascular function, in particular, adult blood pressure (BP). The purpose of this presentation will be to review the evidence that has led to this conclusion, offer ideas about how this potential early-life shaping of subsequent cardiovascular function may come about, and suggest further studies that will be required in order to characterize the mechanisms responsible for these effects.

Aging↗
PubMed1992

Ultrasonic vocalization by rat pups during recovery from deep hypothermia.

Vocalization in the ultrasonic range (USV) has been reported to occur in young rodents in response to isolation, novelty, handling, and cold. Heretofore these calls have been known to occur only in alert, attentive, or emotionally aroused animals. These studies describe the emission of USV by comatose 9- to 10-day-old rat pups during recovery from deep hypothermia. Calling began at 15-18 degrees C core temperature while pups were virtually unresponsive to stimulation. Experimental results describe the patterns of call production in relation to respiration, cardiac function, colonic temperature, and brown adipose tissue thermogenesis. These vocalizations were 32-42 kHz in frequency, reached peak rates of 50/min at 23 degrees C, and were eliminated by laryngeal denervation, thus resembling isolation-induced vocalizations. However, contact with their dams failed to reduce call rates until pups had warmed above 25 degrees C. Newborn and weanling pups also emitted USV in deep hypothermia, but no USV were observed in pups recovering from general anesthesia. The possible functions and evolution of this behavior are discussed.

Adipose Tissue, Brown↗
PubMed1992

Effect of a social companion on the ultrasonic vocalizations and contact responses of 3-day-old rat pups.

Rat pups that are isolated in a novel environment emit ultrasonic calls. Vocalization in 3-day-old pups has been thought to be predominantly under thermal control (Allin & Banks, 1971). By the 2nd week of life, ultrasonic vocalizations are reduced when pups are tested in the company of a single anesthetized littermate (Carden & Hofer, 1990a; Hofer & Shair, 1978). In the present study, it was demonstrated that the vocalization rate of 3-day-old pups is also decreased when an anesthetized littermate is present in the isolation chamber. To determine whether this quieting was a function of the body heat of the companion, in a 2nd experiment, the axillary temperature of the companion was lowered until it was the same as the ambient temperature of the test chamber, 22 degrees C. In the presence of a cool companion, ultrasonic vocalizations were also reduced. For the last experiment, a textured plastic surrogate was substituted for the littermate. Calls were not diminished in the presence of the surrogate.

Animals↗
PubMed1991

Differential effects of specific opioid receptor agonists on rat pup isolation calls.

The possibility was investigated that specific opioid receptor types might selectively alter the production of isolation-induced ultrasonic vocalizations. Intracisternal injections of mu, delta and kappa opioid receptor agonists were administered to isolated 10-day-old rat pups. The mu receptor agonist [D-Ala2-NMe-Phe4-Gly-ol]-enkephalin (DAMGO) and delta receptor agonist [D-Pen2, D-Pen5]-enkephalin (DPDPE) both reduced the rate of isolation-induced ultrasonic calling in the absence of sedation. The kappa receptor agonist U50,488 had the opposite effect, significantly raising the rate of vocalization. Fourteen-day-old pups, with a larger delta receptor population, showed a greater sensitivity to DPDPE than was seen in the younger animals.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗
PubMed1991

Isolation-induced vocalization in Wistar rat pups is not increased by naltrexone.

Rat pups, when removed from dam and littermates and isolated in an unfamiliar milieu, emit a characteristic ultrasonic vocalization that can be quieted by the administration of a nonsedating dose of morphine. Wistar pups, aged 7, 10, 12, 14, or 16 days, were tested after receiving intraperitoneal injections of the opiate antagonist naltrexone (0.0, 0.5, 1.0, or 5.0 mg/kg). The rate of isolation-induced ultrasonic vocalizations was unaffected by naltrexone at any dose, and there were no significant naltrexone-related changes on other behavioral measures. The complexity of the opioid system is discussed, as it may be involved in the vocal reaction to isolation.

Animals↗
PubMed1991

Independence of ultrasonic vocalization and thermogenic responses in infant rats.

Ultrasonic vocalizations (USV) normally accompany brown adipose tissue (BAT) thermogenesis in infant rats exposed to cold. BAT activation (measured by implanted thermistors) was pharmacologically blocked with hexamethonium (20 mg/kg ip) in 12-13-day-old pups, but they nevertheless showed normal USV responses to cold. Activation of BAT in warm pups by norepinephrine (800 micrograms/kg sc) failed to elicit USV. It is concluded that BAT activation is neither necessary nor sufficient for USV production. To evaluate how tightly the two responses may be coupled centrally, rat pups deprived of nutrients for 24 hr, in which sympathetic activation is known to be inhibited centrally (Bignall, Heggeness, & Palmer, 1975), were studied. These pups vocalized with the same latency in response to cold as normals but failed to show evidence of concurrent BAT activation. It is concluded that USV and BAT thermogenesis are normally elicited together by cold but are not tightly linked physiologically.

Adipose Tissue, Brown↗
PubMed1991

Trigeminal and olfactory pathways mediating isolation distress and companion comfort responses in rat pups.

Isolation in a novel test cage elicits ultrasonic vocalization (USV) in 12-13-day-old rat pups, and the presence of an anesthetized littermate companion reduces USV while eliciting body contact. These responses were studied in pups with surgical lesions of trigeminal snout afferents and after olfactory denervation by nasal ZnSO4 perfusion. With lesions of only one system, body contact with the passive companion was reduced by 20%, and interpup orientation was differentially affected by the two types of lesions. However, USV rates were no different from littermate controls in the presence of the companion or when tested alone. Combined lesions of both systems reduced contact time 55% and eliminated any reduction in USV rates by the companion while leaving intact USV and locomotor responses to isolation. These results suggest that different sensory pathways may mediate isolation distress and companion comfort responses.

Animals↗