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

Emissions of ultrasonic vocalizations (USVs) by rat pups (Rattus norvegicus) during hypothermia have consequences for recovery and warming. The effects on dam behavior of USVs emitted by 3- to 11-day-old pups during hypothermia at rectal temperatures between 18 and 22°C was investigated 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. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Dopaminergic modulation of kappa opioid-mediated ultrasonic vocalization, antinociception, and locomotor activity in the preweanling rat.

The purpose of this study was to determine whether dopamine (DA) systems modulate kappa opioid-mediated ultrasonic vocalizations (USVs), antinociception, and locomotion in young rats. Seventeen-day-old rats were injected with the kappa agonist U-50,488 (0.0-7.5 mg/kg) and saline, the D?-like receptor agonist R(-)-propylnorapomorphine (NPA; 0. 1 or 1.0 mg/kg), the indirect DA agonist cocaine (10 or 20 mg/kg), or the DA antagonist flupenthixol (0.25 or 0.5 mg/kg). USVs and locomotion were measured for 6 min, with antinociception being assessed with a tail-flick test. Kappa receptor stimulation produced analgesia and increased USVs and locomotion. U-50,488-induced analgesia was potentiated by NPA, whereas U-50,488-induced USVs were attenuated by both DA agonists. NPA and flupenthixol depressed U-50,488's locomotor effects. These results show that DA systems interact with kappa opioid systems to modulate USVs, antinociception, and locomotion in preweanling rats. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Independence of benzodiazepine and opiate action in the suppression of isolation distress in rat pups.

To determine whether benzodiazepines (BDZs) quiet isolation distress in 10-day-old rat pups by causing a release of endogenous opioids, a blockade of the effects of chlordiazepoxide (CDP) by the opiate antagonist naltrexone (NLX) was sought. Nonsedating doses of morphine (MOR) (0.125 mg/kg) and CDP (2.0 mg/kg) were equally effective in reducing ultrasonic vocalizations and other indices of isolation distress. Appropriate blocking agents NLX (0.5 mg/kg) against MOR and Ro 15-1788 (4.0 mg/kg) against CDP returned distress measures to levels of saline-treated rat pups. However, NLX failed to reverse the quieting effects of CDP. If CDP potentiates endogenous opioid release, then NLX should block the CDP effect. A higher dose of CDP did not reveal a release of endogenous opioids, and a higher dose of NLX did not antagonize CDP. The quieting effects of BDZs on isolation distress do not appear to be mediated by the opiate system. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

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. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

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.     

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. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Sensory control of maternal aggression in Rattus norvegicus..

Three experiments, with nulliparous Wistar rats, investigated the effects of restricted pup exposure and male exposure on maternal aggression and the incidence of olfactory exploration of an intruder by the mother rat. It was found that a decline in maternal aggression occurred when the litter was placed in a glass flask while remaining in the home cage. In contrast, maternal aggression persisted following placement of the pups in a nylon mesh bag. The pups did not vocalize while in the mesh bags, suggesting that olfactory cues from the offspring constitute a critical element in the maintenance of maternal aggression in the rat. It has been suggested that the odor not only of the pups but also of the intruder may contribute to eliciting aggressive behavior in lactating rodents. In line with this proposal, it was found that mother rats spent about one-third of the time preceding the 1st attack sniffing the body of the intruder. In contrast to findings in mice, housing of the prospective intruder behind a double wire mesh partition in the lactating female's home cage failed to reduce her aggressiveness toward him. Rats may require more intimate contact with an individual than do mice for the aggression-reducing effect of familiarization to be observed. (30 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Decreased venous return is neither sufficient nor necessary to elicit ultrasonic vocalisations of infant rat pups.

It has been proposed that all ultrasonic vocalizations (USVs) in young rats are by-products of a cardiovascular response to decreased venous return, the abdominal compression reaction. To test the hypothesis, venous return was decreased in infant rats while USV and cardiovascular measures were monitored. Neither injection of the vasodilator sodium nitroprusside nor blood withdrawal from the superior vena cava or carotid artery elicited USV from pups in their home cage. Thus, decreased venous return by itself is not sufficient to elicit USV. To test whether venous return is a necessary mechanism for USV production, 5% dextrose in water or blood was infused intravenously into isolated pups that were producing USV. This artificial increase of venous return did not affect the rate of USV. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Isolation disrupts retention in preweanling rat pups.

Expression of an olfactory memory in 18-day-old rat pups was examined in eight experiments following brief manipulations of environmental conditions prior to a retention test. In the first experiment we found that retention was disrupted if a pup was placed in isolation for 3 hr prior to the retention test. The retention deficit persisted even when pups had 3-hr exposure to an anesthetized dam and siblings before testing. However, there was no deficit in retention if pups spent the pretest interval with a nonlactating foster dam, their father, or littermates. Finally, we found that this deficit in retention could be alleviated by cuing treatments that preceded the retention test following isolation. Both discrete cues used during training and returning the pup to the home cage with parents and siblings for 3 hr were found to alleviate the retention deficit caused by isolation. These data demonstrate that housing conditions can influence postacquisition memory processes in the young animal. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Molecular cloning and expression of inducible nitric oxide synthase in chick embryonic ventricular myocytes

In order to determine the effect of kappa-opioid receptor agonist on the beta1-adrenoceptor stimulation in the heart, the effects of norepinephrine (NE), a beta1-adrenoceptor agonist, on contraction and electrically induced intracellular calcium ([Ca2+]i) transient in the single rat ventricular myocyte pretreated with a kappa-opioid receptor agonist, trans-(+/-)-3, 4-dichloro-N-methyl-N-(2-[1-pyrrolidinyl]cyclohexyl)-benzeneacetamide (U50,488H), at 0.01-1 microM were studied with a video edge tracker method and a spectrofluorometric method using fura-2 as calcium indicator, respectively. NE at 0.01-10 microM augmented both twitch amplitude and electrically induced [Ca2+]i transient dose-dependently, which were abolished by propranolol at 1 microM, a beta-adrenoceptor antagonist. The effects of NE on both contraction and [Ca2+]i transient were attenuated in a dose-dependent manner by U50,488H at 0.01-1 microM, which itself had no effect at all. The maximum response ( Emax) was decreased, while the concentration that produces 50% of the maximum response (EC50) was enhanced, by U50, 488H. The inhibitory effects of U50,488H on beta-adrenoceptor stimulation were completely blocked by pretreatment with norbinaltorphimine, a specific kappa-opioid receptor antagonist at 1 microM, or preincubation with pertussis toxin (PTX) at 200 ng/ml for 6 h. On the other hand, the inhibition on NE-induced augmentation in electrically induced [Ca2+]i transient by U50,488H was not affected by pretreatment with U73122, a specific inhibitor of phospholipase C (PLC), at 10 microM for 30 min. U50,488H attenuated the augmentation of the electrically stimulated [Ca2+]i transient induced by forskolin at 0.1 and 0.5 microM. It did not, however, affect the augmentation of the electrically induced [Ca2+]i transient by N6, 2'-O-dibutyryl adenosine cyclic monophosphate (DB-cAMP). The results suggest that kappa-opioid receptor stimulation by U50,488H at 10(-6 )M or lower may inhibit the effects of beta-adrenoceptor stimulation by acting at a PTX-sensitive G-protein and AC, but not via the phosphoinositol pathway.     

Phospholipase C inhibitors attenuate arrhythmias induced by kappa-receptor stimulation in the isolated rat heart

To determine whether the phospholipase C (PLC)/inositol 1,4,5 trisphosphate (IP3)/Ca2+ pathway mediates cardiac arrhythmias induced by kappa-opioid receptor stimulation, the effects of U50,488H, a selective kappa-opioid receptor agonist, on cardiac rhythm in a isolated perfused rat heart, intracellular calcium ([Ca2+]i) in a single ventricular myocyte and IP3 production in myocytes were studied in the presence and absence of PLC inhibitors. U50,488H, the effects of which had been shown to be abolished by a selective kappa-receptor antagonist, nor-binaltorphimine, induced arrhythmias dose-dependently and increased both [Ca2+]i and IP3-production in the heart. More importantly, the effects of U50,488H were blocked by PLC inhibitors, neomycin and streptomycin. To further confirm the selectivity of action of the PLC inhibitor, the effects of another PLC inhibitor U73122 and its inactive structural analog, U73343, on cardiac rhythm in the isolated perfused rat heart were compared. The former did, while the latter did not, block the arrhythmogenic effect of U50,488H. We also determined whether the effects of kappa-receptor stimulation involves a pertussis toxin (PTX)-sensitive G-protein. We found that pretreatment with PTX at 4 microg/l for 10 min, a treatment shown to affect PTX sensitive G-protein-mediated functions, attenuated significantly the U50,488H-induced arrhythmias. The present study provides evidence that kappa-receptor stimulation-induced cardiac arrhythmias involves, at least partly, the PLC/IP3/Ca2+ pathway as well as a PTX sensitive G-protein.     

Separable Brainstem and Forebrain Contributions to Ultrasonic Vocalizations in Infant Rats.

Competing views persist concerning the functional significance of ultrasonic vocalizations (USVs) emitted by infant rats. One perspective holds that USVs result from an emotional state of fear and anxiety, the adult expression of which depends in part on forebrain mechanisms. Here the authors examine whether pups lacking forebrain input are capable of emitting USVs. Aspirations of neocortex and hippocampus or precollicular decerebrations were performed on 8-day-old rats. After the rats recovered, USV responses were recorded for 10 min at room temperature (Phase 1) followed by enhanced cooling for 20 min (Phase 2). Experimental pups emitted significantly fewer USVs than shams during Phase 1 but vocalized at similar rates during Phase 2. Thus, in infants, brainstem neural circuitry is sufficient to support emission of USVs. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Cannabinoid modulation of rat pup ultrasonic vocalizations

The present study investigated the effects of the cannabinoid receptor agonist CP 55,940 (1-)-cis-3-[2-hydroxy-4-(1,1-dimethylheptyl) phenyl]-trans-4-(3-hydroxypropyl)cyclohexanol) and the cannabinoid receptor antagonist SR 141716A (N-(piperidin-l-yl)-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-me thyl-1 H-pyrazole-3-carboxamide hydrochloride) on ultrasonic vocalizations, body temperature and activity in 11-13-day-old rat pups. Testing occurred in a 5-min session 30 min following drug administration. CP 55,940 produced a dose-dependent decrease in ultrasonic vocalizations, with a 1000-micrograms/kg dose causing an almost complete inhibition of calls. Doses of 100 and 1000 micrograms/kg of CP 55,940, but not 10 micrograms/kg, caused significant hypothermia in the pups and the 1000 micrograms/kg dose also inhibited activity. The cannabinoid receptor antagonist SR 141716A (20 mg/kg) reversed the effects of 1000 micrograms/kg CP 55,940 on ultrasonic vocalizations and body temperature, but the benzodiazepine receptor antagonist flumazenil (20 mg/kg), the dopamine D1 receptor antagonist SCH 23390 (0.5 mg/kg) and the opioid receptor antagonist naloxone (1 mg/kg) did not. When administered alone, SR 141716A (20 mg/kg) increased pup ultrasonic vocalizations without affecting body temperature or activity. These results indicate that cannabinoids modulate ultrasonic vocalization production in rat pups in a manner that is independent of hypothermia. The increase in ultrasonic vocalizations produced by SR 141716A is one of the first reported behavioural effects of this drug and suggests that the endogenous cannabinoid ligand anandamide may be involved in the regulation of ultrasonic vocalizations.     

Ontogenetic differences in the expression of conditioned stimulus conditioning: effects of retention interval

Preweanling 17-day-old rats were tested for retention of the conditioned emotional response after a 5-min or 24-hr retention interval. For a variety of conditioning parameters (i.e., variation in conditioned stimulus modality, unconditioned stimulus intensity, number of training trials), conditioned responding was consistently weaker after 5 min than after 24 hr. This apparent "incubation," or "hypermnesic," effect was not found in adult rats, even when comparable conditioning levels were indicated on the 24-hr test. The transient short-term retention deficit observed in 17-day-old preweanlings was alleviated by placing the pup in its home cage during the 5-min retention interval or by extending the conditioning session. Fifteen-day-old rat pups did not benefit from home cage exposure or extended training and displayed the transient short-term retention deficit regardless. The results are discussed in terms of age-related effects on time-dependent memory consolidation.     

Factors influencing cortisol and behavioral responses to maternal separation in guinea pigs.

Infant guinea pigs recently were found to respond to brief maternal separation with an increase in plasma cortisol (COR) levels. The present experiments were conducted to further characterize this response and compare it with the COR separation response previously observed in primates. In Exp 1, separation of guinea pig pups from their mothers did not elevate the plasma COR levels of the pups at either 30 or 180 min when they remained alone in their home cages during the separation. Exp 2 showed that COR levels of pups placed alone in a novel cage were greater at 30, 90, and 180 min than were those of pups placed in the cages together with their mothers. In contrast, the separated pups vocalized more than did pups tested with their mothers during the initial 30 min only. In Exp 3, pups raised on inanimate surrogates responded less intensely to rearing-figure separation in terms of COR and vocalizations than did mother-reared controls. Results indicate differences (response to home cage separation) and similarities (dissociation of COR and vocalization responses, effect of surrogate separation) in the separation responses of guinea pig and primate infants. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Dietary isoflavones reduce plasma cholesterol and atherosclerosis in C57BL/6 mice but not LDL receptor-deficient mice

To assess the cardiovascular effects of systemically administered opioid agonists, changes in blood pressure and heart rate were observed after intravenous (i.v.) administration of U50,488H (trans-3,4-dichloro-N-[2-(1-pyrrolidinyl) cyclohexyl]benzeneacetamide), a selective kappa-opioid receptor agonist, and DAMGO (D-Ala2, N-Me-Phe4, Gly5-ol), a selective mu-opioid-receptor agonist. Intravenous administration of U50,488H (1.2 mg/kg) and DAMGO (0.3 mg/kg) to the awake sheep resulted in an immediate increase in blood pressure. The pressor response to U50,488H was accompanied by an increase in heart rate. In contrast, there was no accompanying change in heart rate in response to DAMGO. We hypothesized that the lack of a reflex bradycardia to the pressor responses of both the mu- and kappa-opioid-receptor agonists was due to a blunting of baroreflex-mediated bradycardia. The reflex bradycardia to norepinephrine (0.6 microg/kg/min) was significantly reduced in the presence of DAMGO but not U50,488H. In view of the lack of effect of U50,488H on the baroreflex, we further hypothesized that the tachycardia it elicited was due to an increase in sympathetic activity. Pretreatment with propranolol (0.1 mg/kg) completely blocked the tachycardia elicited by U50,488H. These data suggest that the lack of a reflex bradycardia to the pressor response of DAMGO is due to a blunting of baroreflex-mediated bradycardia. In contrast, the increase in heart rate caused by U50,488H is mediated by sympathetic activation of the heart.     

The kappa opioid receptor expressed on the mouse R1.1 thymoma cell line down-regulates without desensitizing during chronic opioid exposure

The R1.1 mouse thymoma cell line expresses a single class of kappa opioid receptors that is negatively coupled to adenylyl cyclase through a Bordetella pertussis toxin-sensitive inhibitory guanine nucleotide-binding protein. The aim of the present study was to determine whether chronic opioid treatment of R1.1 cells altered either the binding properties or the functional response associated with the kappa opioid receptor. Culturing of R1.1 cells with the kappa-selective agonist (trans)-3,4-dichloro-N-methyl-N-[2-(1-pyrrolidinyl)-cyclohexyl] benzeneacetamide methane-sulfonate hydrate (U50,488) for 3 hr and longer, followed by extensive washing of R1.1 cell membranes, produced a concentration- and time-dependent reduction in the binding of the kappa-selective ligand (5 alpha,7 alpha,8 beta)-(-)-N-methyl-N-(7-(1-pyrrolidinyl)-1- oxaspiro(4,5)dec-8-yl) benzeneacetamide ([3H]U69,593). Culturing of R1.1 cells with 100 nM U50,488 for 24 hr produced approximately a 50% reduction in the Bmax value for [3H]U69,593 and [3H]naloxone binding. In contrast to the reduction in binding, there was no change in the inhibition of adenylyl cyclase activity by (-)-U50,488. To determine whether kappa opioid receptor function was maintained by spare receptors after agonist-induced down-regulation, membranes from untreated R1.1 cells were incubated with 400 nM of the irreversible opioid antagonist beta-chlornaltrexamine (beta-CNA) followed by extensive washing. beta-CNA produced a 50% reduction in the [3H]U69,593 binding and a 6-fold increase in the IC50 value for (-)-U50,488 inhibition of adenylyl cyclase activity, with no change in the maximal inhibition of cyclic AMP levels.(ABSTRACT TRUNCATED AT 250 WORDS)     

Monoamine activity in anterior hypothalamus of guinea pig pups separated from their mothers.

Brief isolation in a novel environment increased the ratios of 3-methoxy-4-hydroxyphenylethylene glycol to norepinephrine (MHPG:NE) and dihydroxyphenylacetic acid to dopamine (DOPAC:DA) in the anterior hypothalamus of 44 guinea pig pups. Ratios were significantly elevated after 90 min of isolation and for MHPG:NE, after 30 min of isolation; changes were due to increases in MHPG and DOPAC. Home cage isolation produced no change in any measure of catecholamine activity. No changes in levels of serotonin or its metabolite were observed. In Exp 1, resting levels of NE and DOPAC:DA were predictive of the rate of separation-induced vocalization. Maternal separation in the context of novelty increases hypothalamic NE and DA activity; however, both isolation and novelty are required because neither maternal separation in the home cage nor exposure to a novel cage together with the mother had any discernible effect. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Paradoxical effects of kappa-opioid stimulation on the locomotor activity and Fos immunoreactivity of the preweanling rat: role of dopamine receptors

The kappa-opioid agonist U-50,488 increases the locomotor activity of preweanling rats. The authors attempted to determine whether this effect was modulated by dopamine (DA) system functioning. Surprisingly, U-50,488's locomotor activating effects were attenuated by both the DA receptor antagonist flupenthixol and the DA receptor agonist R(-)-propylnorapomorphine (NPA). In order to determine those brain areas stimulated by U-50,488, Fos immunoreactivity was assessed in 17- and 80-day-old rats. U-50,488 not only enhanced the locomotor activity of the younger rats, but it also enhanced Fos expression in various brain areas, including the nucleus accumbens and medial striatum. NPA blocked U-50,488-induced Fos expression in the latter region. When considered together, these results indicate that U-50,488 does not increase locomotion by stimulating a DA mechanism. Instead, either agonizing or antagonizing DA receptors is sufficient to disrupt U-50,488's locomotor activating effects in the preweanling rat.     

Retention of maternal behavior in nulliparous and primiparous rats: Effects of duration of previous maternal experience.

Lactating primiparous and nonlactating pup-induced maternal nulliparous female CD rats were given 1, 4, or 9 days of maternal experience with rat pups before they were isolated from the young. 25 days later, Ss were reexposed to 3–8 day old foster pups, and latencies to show maternal behavior in the home cage and a T-maze test were scored. In the home cage, the latencies of all nulliparous groups were shorter upon reinduction. Comparisons of primiparous and nulliparous groups revealed that primiparous females (1, 4, and 9 days combined) carried a pup, crouched, retrieved, and grouped the pups and built a good nest faster than did nulliparous females (combined groups). The number of behavioral differences between specific primiparous and nulliparous groups decreased as the length of prior maternal experience increased. In the T-maze, latencies to retrieve a pup were shorter in primiparous females. Results indicate that the processes underlying establishment of the long-term retention of short-latency maternal behavior in these groups may be comparable. (20 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)