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.     

Ventral striatum dopamine D2 receptor activity inhibits rat pups' vocalization response to loss of maternal contact.

Most mammalian infants vocalize when isolated. The vocalization promotes caregiver proximity, which is critical to survival. If, before isolation, a rat pup has contact with its dam, its isolation vocalization rate is increased (maternal potentiation) relative to isolation preceded only by littermate contact. Prior work showed that systemic administration of a D2 receptor agonist blocks maternal potentiation at doses that do not alter baseline vocalization. In this study, infusion of quinpirole (2 μg/side) into the nucleus accumbens also blocks maternal potentiation. Infusion of the accumbens with the D2 antagonist raclopride (4 μg/side) prevents systemic quinpirole from blocking potentiation. Quinpirole infusion in the dorsal striatum did not affect maternal potentiation and infusion of raclopride in the dorsal striatum did not reverse the block of maternal potentiation by systemic quinpirole. Vocalization results after a second vehicle infusion on a given day are no different than the results following an initial vehicle infusion, so experimental design can not account for the effects of drug infusions. Because activity level was increased by both dorsal and ventral striatum infusions, activity level can not account for the results. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Maternally modulated infant separation responses are regulated by D2-family dopamine receptors.

Although dopamine is necessary for mammalian adult pair-bond formation and maternal behavior, its function in infant social behavior and attachment has been less thoroughly explored. The vocalization rate of an isolated rat pup is influenced by recent social contact. Interactions with the dam potentiate vocalization rate. Interactions with littermates or adult males do not. Systemic administration of the D2-family agonist quinpirole specifically blocked maternal potentiation at doses that did not alter vocalization rate in an isolation prior to dam contact. This result was not explained by quinpirole's effects on body temperature or locomotion. The results are consistent with a role for dopamine in infant social behavior. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Demonstrations of neophobia and enhanced neophobia in the albino rat.

Studied the conditions under which neophobia and enhanced neophobia occur in the albino rat in 5 experiments with a total of 160 male albino rats. Neophobia to a .1% saccharin solution was demonstrated in a 10-min single-bottle test. This neophobia was enhanced by pairing water ingestion with a radiation exposure of 100 r or an injection of LiCl 24 hrs prior to the saccharin test. In addition, it was found that the differences in consumption of saccharin in a 10-min single-bottle test due to neophobia and enhanced neophobia were produced by consistent differences in drinking rates which appeared early in the 10-min period. The disappearance of neophobia and enhanced neophobia in a 1-hr single-bottle test suggested that the effects of neophobia and enhanced neophobia are short-lived and are best measured in a brief single-bottle test. Enhanced neophobia was not found when 2 days of water drinking were interposed between LiCl poisoning and saccharin testing. (22 ref) (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)     

Colorectal cancer in the Royal Navy--an opportunity to intervene?

Whole-cell recordings were made in the nucleus tractus solitarii (NTS) in transverse brainstem slices from rats. Monosynaptic GABAA-receptor-mediated inhibitory postsynaptic currents (IPSCs) or potentials (IPSPs) were evoked (0.1-0.2 Hz) by electrical stimulation within and medial to the tractus solitarius in the presence of the ionotropic glutamate receptor antagonists 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX; 10 microM) or 6,7-dinitroquinoxaline-2,3-dione (DNQX; 10 microM) and D-amino-5-phosphonopentanoic acid (APV; 50 microM). A brief period of tetanic stimulation (20 Hz, 2 s) resulted in posttetanic (< 5 min, 69 of 73 recordings) and sustained potentiation (> 15 min, 31 of 73 recordings) of the IPSP/Cs. Sustained potentiation was not due to alterations in the reversal potential of IPSP/Cs. Both pre- and post-tetanus IPSP/Cs were completely blocked by the GABAA antagonist bicuculline (10 microM). Postsynaptic responses to pressure ejection of the GABAA-receptor agonist muscimol were unaltered in cells displaying sustained potentiation. Sustained potentiation of IPSP/Cs could be induced by tetanus in the presence of either metabotropic glutamate receptor antagonists or bicuculline. However, sustained potentiation could not be induced in the presence of the GABAB-receptor antagonists 2-OH-saclofen (400 microM) or CGP35348 (3-amino-propyl-(diethoxymethyl)phosphinic acid, 100 microM), although a subsequent tetanus following washout induced sustained potentiation. Posttetanic potentiation was unaffected by GABAB-receptor antagonists. These data suggest that neuronal or terminal excitability of GABAergic interneurons in the NTS is enhanced following brief periods of increased frequency of activation in vitro. This novel phenomenon within the rat medulla may be involved in the temporal modulation of autonomic reflex sensitivity observed during certain behavioral states, such as the defense reaction.     

Subunit-specific interactions of cyanide with the N-methyl-D-aspartate receptor

Cyanide can potentiate N-methyl-D-aspartate receptor-mediated physiological responses in neurons. Here we show that this phenomenon may be attributable to a subunit-specific chemical modification of the receptor directly by the toxin. N-Methyl-D-aspartate (30 microM)-induced whole cell responses in mature (22-29 days in vitro) rat cortical neurons were potentiated nearly 2-fold by a 3-5-min treatment with 2 mM potassium cyanide, as did a similar treatment with 4 mM dithiothreitol. A 1-min incubation with the thiol oxidant 5,5'-dithiobis(2-nitrobenzoic acid) (0.5 mM) readily reversed the potentiation induced by either cyanide or dithiothreitol. Cyanide did not increase further currents previously potentiated by dithiothreitol nor was it able to potentiate responses during brief co-application with the agonist. Transient expression studies in Chinese hamster ovary cells with wild-type and mutated recombinant N-methyl-D-aspartate subunits (NR) demonstrated that cyanide selectively potentiated NR1/NR2A receptors, presumably via the chemical reduction of NR2A. In contrast, currents mediated by NR1/NR2B receptors were somewhat diminished by the metabolic inhibitor. Some of the effects of cyanide on NR1/NR2B receptors may be mediated by the formation of a thiocyanate adduct with a cysteine residue located in NR1. Cyanide thus is able to distinguish chemically between two different N-methyl-D-aspartate receptor subtypes and produce diametrically opposing functional effects.     

Effects of d-amphetamine on responding of squirrel monkeys maintained under second-order schedules of food presentation, electric shock presentation or stimulus-shock termination

The effects of d-amphetamine (0.01-5.6 mg/kg i.m.) were studied on lever pressing of squirrel monkeys maintained under various second-order schedules by a visual stimulus (S) that, with separate monkeys, was occasionally paired with the presentation of either food, electric shock or with the termination of a stimulus in the presence of which shocks occurred. Under one condition, the first response after 5 min produced a 3-sec stimulus change and the fourth stimulus change was followed immediately by food delivery, electric shock presentation or by the termination of a stimulus in the presence of which shocks occurred [fixed-ratio (FR); fixed-interval (FI) [FR 4 (FI 5-min:S)]. The effects of d-amphetamine were also studied under the food- and shock-presentation schedules when food or shock occurred only once, at the end of each session, after completion of 53n 3-min fixed-intervals all of which ended with a brief stimulus change [FR 10 (FI 3-min : S)]. Under a third condition, each thirtieth response produced the 3-sec brief stimulus (FR 30 : S) and the first FR 30 completed after 5 min elapsed produced the stimulus followed by food or, with separate monkeys, electric shock [FI 5-min (FR 30:S)]. Low to intermediate doses of d-amphetamine (0.03-0.3 mg/kg) generally increased and higher doses (0.56-5.6 mg/kg) decreased responding under all conditions. The effects of d-amphetamine on responding maintained by brief stimuli under different types of second-order schedules are generally similar, regardless of the type of reinforcing event or particular second-order schedule.     

Changes in self-stimulation at stimulation-bound eating and drinking sites in the lateral hypothalamus during food or water deprivation, glucoprivation, and intracellular or extracellular dehydration.

Examined the effects of hunger induced by food deprivation, 2-deoxy-{d}-glucose (200 mg/kg), or insulin (2 U/kg) and thirst induced by water deprivation, sodium chloride (4 M), or polyethylene glycol (5 ml of 30% w/w) on lateral hypothalamic self-stimulation in 40 male Long-Evans rats. Changes in self-stimulation were evaluated at electrodes that produced stimulation-bound eating and/or drinking or neither behavior. Daily 30-min test sessions consisted of 3 5-min periods of self-stimulation alternated with 3 5-min periods when barpresses resulted in 5-sec time-out from experimenter-delivered stimulation (stimulation escape). Food deprivation significantly increased self-stimulation; insulin, 2-deoxy-{d}-glucose, and sodium chloride significantly suppressed self-stimulation; water deprivation mildly inhibited self-stimulation; and polyethylene glycol had no effect. This pattern of findings was noted at electrodes that did and those that did not elicit eating and/or drinking. Findings do not support the hypothesis that the magnitude of lateral hypothalamic self-stimulation is differentially and predictably controlled by specific drive mechanisms indexed by the consummatory behaviors also elicited by the stimulation. (41 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Differential effect of ketamine on the reference and working memory versions of the Morris water maze task.

The assumption that blockade of long-term potentiation by N-methyl-D-aspartate antagonists interferes with spatial memory was supported by experiments showing that 15 mg/kg ketamine impairs acquisition of navigation to a hidden platform but not to a visible platform. Higher doses were required to impair retrieval of overtrained place navigation. In a working memory version of the task, retrieval latencies were shorter than acquisition latencies with 4- to 15-min but not with 30- and 60-min delays. Latent learning was only effective with the 4-min delay. Ketamine prolonged the initial search of the hidden platform at 3 mg/kg and impaired latent learning but not active acquisition at 1.5–20 mg/kg. Comparison of behavioral and synaptic effects of ketamine suggests that long-term potentiation is a necessary condition, but not a sufficient condition, for acquisition of place navigation, because search strategy and latent place learning are impaired by ketamine doses not interfering with this synaptic phenomenon. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Maternal deprivation potentiates pituitary-adrenal stress responses in infant rats.

Examined the effect of maternal deprivation on the pituitary-adrenal response of 12-, 16-, and 20-day-old rat pups to novelty stress. Infants were either deprived individually in heated incubators or left in the home nest with their mother and then tested for corticosteroid response to 30-min exposure to a novel test arena. In Exp 1, the magnitude of the stress response (SR) was a positively accelerated function of the deprivation interval. SRs were not increased after 1 hr of deprivation, were modestly increased after 8 hrs of deprivation, and were dramatically increased after 24 hrs of deprivation. Exp 2 investigated whether potentiation of the SR resulted from the maternal or the nutritive components of the deprivation procedure. Pups were tested under 1 of 4 treatment conditions formed by a 2 (Maternally Deprived vs Nondeprived)?×?2 (Nutritively Deprived vs Nondeprived) factorial design. At 12 and 16 days of age, potentiation of the SR was traced to the absence of maternal care and not nutrients. At 20 days of age, both maternal and nutritive deprivation contributed to the potentiated SR. Exp 3 showed that this effect was mediated by increased adrenocortical sensitivity to ACTH, because the corticosteroid response to exogenous ACTH administration was also increased by maternal deprivation. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The Uba2 and Ufd1 proteins of Saccharomyces cerevisiae interact with poly(A) polymerase and affect the polyadenylation activity of cell extracts

We investigated calcium influx in the long lasting potentiation induced in area CA1 of rat hippocampus by brief bath application of the G-protein activator A1F4-(NaF/AlCl3). Brief (10 min) bath application of A1F4 in standard saline (with 2 mM Ca2+) consistently induced a long lasting potentiation which was not observed if A1F4 was bath-applied in nominally calcium free saline. Increasing the potential calcium influx, either by raising extracellular calcium concentration to 3.5 mM or by addition of the voltage operated calcium channel (VOCC) agonist BayK8644, failed to increase the number of slices exhibiting potentiation or the mean level of potentiation. Bath application of AlF4 in the presence of the VOCC antagonist failed to block the potentiation and A1F4- readily induced a long lasting potentiation under voltage clamp conditions, strongly suggesting that the calcium influx required for A1F4-induced potentiation is not through NMDA receptors or VOCC channels. It is suggested that the calcium required may be provided by an ongoing recharging and emptying of IP3 sensitive intracellular Ca2+ stores.     

Infant-mother recognition in a social rodent (octodon degus).

Octodon degus (degu), a biparental species with precocious offspring is a potential model for the study of social attachment and related affective disorders such as depression. This study investigates the nature of the social bond between young degus and their mothers with a special emphasis on infant-mother recognition. We tested young degus in a potentiation paradigm to determine if social contact, particularly with the mother, can modulate an infant's vocal response to isolation. One week later, animals were presented with a choice between their mother and an unfamiliar female or a sample of familiar and unfamiliar nesting materials. Subsequently, the ability of whole litters to discriminate between their mother and unfamiliar females was tested. We observed that infant degus alter their isolation response after brief social contact. Degu infants readily distinguish between familiar and unfamiliar nesting materials but fail to differentiate between their mother and unfamiliar females in an identical setting. Nevertheless, entire litters show a preference for their mothers when tested similarly in a group, demonstrating a perhaps socially facilitated ability to recognize the biological mother at an early age. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

A convenient and inexpensive chemo-radiosensitivity assay for lung cancer cells using Terasaki''s microplate

Pharyngeal dilator muscles are critical for maintaining upper airway patency in the neonatal period. The present study examined in vitro the contractile properties of a pharyngeal dilator muscle, the sternohyoid, in 1-7-day-old piglets (n = 24). Isometric contraction and half-relaxation times were 36.7 +/- 1.1 and 30.9 +/- 1.2 msec, respectively. Twitch potentiation ('staircase phenomenon') and post-tetanic potentiation were noted following repetitive stimulation. During prolonged repetitive stimulation with a standard (40 Hz) fatigue test, muscle force declined gradually over time, with loss of half of the initial force occurring over 138 +/- 11 sec, and a 2-min fatigue index (ratio of force at 2 min to initial force) of 0.52 +/- 0.03. An additional 10 piglets were studied at ages of 14-20 days. Muscle from older piglets had comparable isometric twitch kinetics as that of younger animals. However, sternohyoid muscle from the older piglets had worse endurance than muscle from the younger animals, as indicated by a shorter time required for force to decrease by half (86 +/- 10 sec, P < 0.01) and a lower 2-min fatigue index (0.36 +/- 0.03, P < 0.01). These data indicate that for the sternohyoid muscle of the newborn piglet (a) physiological properties are consistent with moderate to fast contraction with good endurance, (b) force potentiates during repetitive twitch stimulation and following a brief period of tetanic stimulation, and (c) there is worsening of endurance but no change in isometric twitch kinetics with increasing age during the first weeks of life.     

Behaviorally functional opioid systems in infant rats: II. Evidence for pharmacological, physiological, and psychological mediation of pain and stress.

Two experiments, with 160 10-day-old Sprague-Dawley rat pups, examined the behavioral characteristics of the neonatal opioid system during distressful situations, using a modification of the hot-plate paw-lick test. Ss were analgesic to heat following intraperitoneal morphine (0.5 mg/kg). Subcutaneous naloxone (0.5 mg/kg) prevented the analgesia. Morphine analgesia was significantly greater in Ss group-isolated from the dam. Saline controls group-isolated from the dam exhibited longer latencies than their nest-housed siblings. Individual isolation for 5 min markedly increased paw-withdrawal latency, and this effect was naltrexone reversible. Analgesia was not seen when Ss were tested directly from the nest or when grouped with others for 5 min. It is suggested that the opioid systems for stress and pain are functional in 10-day-old rats and that short-term isolation from the dam is a probable natural stressor modulated by endogenous opioid release. (51 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Functional consequences of lidocaine binding to slow-inactivated sodium channels

Na channels open upon depolarization but then enter inactivated states from which they cannot readily reopen. After brief depolarizations, native channels enter a fast-inactivated state from which recovery at hyperpolarized potentials is rapid (< 20 ms). Prolonged depolarization induces a slow-inactivated state that requires much longer periods for recovery (> 1 s). The slow-inactivated state therefore assumes particular importance in pathological conditions, such as ischemia, in which tissues are depolarized for prolonged periods. While use-dependent block of Na channels by local anesthetics has been explained on the basis of delayed recovery of fast-inactivated Na channels, the potential contribution of slow-inactivated channels has been ignored. The principal (alpha) subunits from skeletal muscle or brain Na channels display anomalous gating behavior when expressed in Xenopus oocytes, with a high percentage entering slow-inactivated states after brief depolarizations. This enhanced slow inactivation is eliminated by coexpressing the alpha subunit with the subsidiary beta 1 subunit. We compared the lidocaine sensitivity of alpha subunits expressed in the presence and absence of the beta 1 subunit to determine the relative contributions of fast-inactivated and slow-inactivated channel block. Coexpression of beta 1 inhibited the use-dependent accumulation of lidocaine block during repetitive (1-Hz) depolarizations from -100 to -20 mV. Therefore, the time required for recovery from inactivated channel block was measured at -100 mV. Fast-inactivated (alpha + beta 1) channels were mostly unblocked within 1 s of repolarization; however, slow-inactivated (alpha alone) channels remained blocked for much longer repriming intervals (> 5 s). The affinity of the slow-inactivated state for lidocaine was estimated to be 15-25 microM, versus 24 microM for the fast-inactivated state. We conclude that slow-inactivated Na channels are blocked by lidocaine with an affinity comparable to that of fast-inactivated channels. A prominent functional consequence is potentiation of use-dependent block through a delay in repriming of lidocaine-bound slow-inactivated channels.     

Maternal separation alters social odor preference development in infant mice (Mus musculus).

This study examined whether daily periods of maternal separation during the first two weeks of life would decrease attraction to familiar nest odors in CD-1 mice 10 and 14 days old. We also investigated whether placing a group of mice (Mus musculus) in nest shavings during the 180-min separation period would mitigate possible separation-induced deficits. The maternal separation procedure has been widely used as a rodent model for the effects of inconsistent or inadequate early caretaking on human development. From postnatal day (PND) 1 to 14, litters were separated from the dam, but not littermates for either 15 or 180 min, or were facility-reared controls. Control, facility-reared mice preferred home-cage nest to clean familiar shaving odors on PND 10, but not PND 14. In contrast, home-cage nest odors attracted maternally separated mice on both test days. Our results suggest that maternal separation maintains the olfactory tether to the nest in a period when the attraction normally begins to weaken. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Response suppression to a shock-predicting stimulus in differentially reared monkeys (Macaca mulatta).

Four rhesus monkeys reared in social isolation for the 1st 9 mo of life and 4 monkeys reared with social contact were trained to leverpress for food reinforcement on a VI 60-sec schedule of reinforcement as adults. A 3-min auditory CS that terminated with the delivery of an electric foot shock was then presented at random intervals during each test session. Results indicate that though preshock response rates did not differ, the isolates failed to suppress responding in the presence of the shock-predicting CS at the same rate or to the same degree as did socially reared Ss. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Morphine enhancement of sucrose palatability: analysis by the taste reactivity test

The ability of morphine to modify sucrose palatability was assessed by the taste reactivity test. In Experiment 1, rats were injected with morphine (0.0, 0.5, 2.0, and 10.0 mg/kg, subcutaneously), 30 min before receiving a 10-min intraoral infusion of 2% or 20% sucrose solution. A dose of 2.0 mg/kg morphine enhanced ingestive reactions elicited by both concentrations of sucrose solution. In Experiment 2, the interval between morphine pretreatment and the taste reactivity test was manipulated. Rats given 2.0 mg/kg morphine 30 or 120 min before testing displayed enhanced ingestive reactions elicited by 20% sucrose solution during the first 5 min of a 10-min test. The results support the hypothesis that morphine enhances the hedonic assessment of sucrose solution.     

Within-subjects positive and negative contrast effects in rats.

Conducted 4 experiments, using a total of 47 Sprague-Dawley albino rats. Ss were given alternating 1-min access periods to 2 tubes containing either 32 or 4% sucrose solutions for daily 6-min test sessions. Lick rate for 32% was higher under comparison (32 vs 4) than noncomparison (32 vs 32) conditions; and lick rate for 4% was lower under comparison conditions (4 vs 32) than under noncomparison conditions (4 vs 4). All sucrose conditions were varied within Ss, and both positive and negative contrast were obtained with a small n. In addition to lick rate, intake and latency measures revealed contrast effects. Deprivation conditions altered latency but not lick rate measures of contrast. Reducing the test session to 3 min (alternating 30-sec access periods) did not greatly affect contrast. Additional experiments provided evidence for distinct within- and between-days contrast effects, as well as a between-groups contrast effect. (22 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)