Behavior In Laboratory Rats Research Articles

Short communication: Do the tameness of the dams and the sex of the offspring have an influence on the “gentling” effect in laboratory rats?

“Gentling” (soft touching, “taming”) has long-term effects on the behavior of laboratory rats (Rattus norvegicus). Our own studies showed that the use of a “gentling” program in the fourth and fifth week of life resulted in a significant reduction in fear behavior towards humans up to the age of 6 months. However, our investigations have so far only considered female animals. In the current study, we therefore wanted to determine whether there also is a long-lasting “gentling” effect in male rats. In addition, we intended to investigate whether there is an impact depending on the level of tameness of the mothers. We mated 14 female rats, which we selected from our previous experiments based on their behavior, with one male rat. Five females became pregnant and had litters (2 “tame” dams had 13 pups and 3 “not tame” dams had 18 pups). The 31 pups (16 female and 15 male rats) were divided into a “gentling” group (n = 16) and a “not gentled” group (n = 15). The previously developed “gentling” program was applied to the “gentling” group. That means the pups were gently touched, hand-fed and talked to during their fourth and fifth week of life (10 minutes per cage twice daily over a period of 14 days). The “not gentled” group did not receive any treatment. To evaluate the “gentling” effect on tameness, behavior tests according to our previous study were performed at the ages of 6, 8, 10, 14 and 16 weeks and 6 months. The experiments were blinded regarding parentage and treatment. The behavior tests revealed that the “gentled” rats were “tamer” than the “not gentled” rats. With Westfall correction for multiple testing, the estimated significant differences lasted up to the 30th week of life and therefore exceeded the results of our previous study. The “gentled” pups of the “tame” dams rendered better results than the “gentled” pups of the “not tame” dams. The female rats improved with increasing age and test experience, but the male rats did not. The results show that this “gentling” program reduces the fear of humans even in male laboratory rats and that the tame nature of the mothers affects the “gentling” effect in the offspring.

A new approach to assess gambling-like behavior in laboratory rats: using intracranial self-stimulation as a positive reinforcer.

Pathological gambling is one manifestation of impulse control disorders. The biological underpinnings of these disorders remain elusive and treatment is far from ideal. Animal models of impulse control disorders are a critical research tool for understanding this condition and for medication development. Modeling such complex behaviors is daunting, but by its deconstruction, scientists have recapitulated in animals critical aspects of gambling. One aspect of gambling is cost/benefit decision-making wherein one weighs the anticipated costs and expected benefits of a course of action. Risk/reward, delay-based and effort-based decision-making all represent cost/benefit choices. These features are studied in humans and have been translated to animal protocols to measure decision-making processes. Traditionally, the positive reinforcer used in animal studies is food. Here, we describe how intracranial self-stimulation can be used for cost/benefit decision-making tasks and overview our recent studies showing how pharmacological therapies alter these behaviors in laboratory rats. We propose that these models may have value in screening new compounds for the ability to promote and prevent aspects of gambling behavior.

Magnetic field polarity fails to influence the directional signal carried by the head direction cell network and the behavior of rats in a task requiring magnetic field orientation.

Many different species of animals including mole rats, pigeons, and sea turtles are thought to use the magnetic field of the earth for navigational guidance. While laboratory rats are commonly used for navigational research, and brain networks have been described in these animals that presumably mediate accurate spatial navigation, little has been done to determine the role of the geomagnetic field in these brain networks and in the navigational behavior of these animals. In Experiment 1, anterior thalamic head direction (HD) cells were recorded in female Long-Evans rats while they foraged in an environment subjected to an experimentally generated magnetic field of earth-strength intensity, the polarity of which could be shifted from one session to another. Despite previous work that has shown that the preferred direction of HD cells can be controlled by the position of familiar landmarks in a recording environment, the directional signal of HD cells was not influenced by the polarity of the magnetic field in the enclosure. Because this finding could be attributed to the animal being insensitive or inattentive to the magnetic field, in Experiment 2, rats were trained in a choice maze task dependent on the ability of the animals to sense the polarity of the experimentally controlled magnetic field. Over the course of 28 days of training, performance failed to improve to a level above chance, providing evidence that the spatial behavior of laboratory rats (and the associated HD network) is insensitive to the polarity of the geomagnetic field.

Effects of noradrenergic alpha-2 receptor antagonism or noradrenergic lesions in the ventral bed nucleus of the stria terminalis and medial preoptic area on maternal care in female rats

Maternal behavior in laboratory rats requires a network of brain structures including the ventral bed nucleus of the stria terminalis (BSTv) and medial preoptic area (mPOA). Neurotransmitter systems in the BSTv and mPOA influencing maternal behaviors are not well understood, although norepinephrine is an excellent candidate because the BSTv contains the densest noradrenergic fiber plexus in the forebrain and norepinephrine in the mPOA is known to influence other female reproductive functions. We hypothesized that downregulated noradrenergic activity in the BSTv and mPOA is necessary for mothering. Postpartum mother-litter interactions were observed after BSTv infusion of yohimbine (an α2 autoreceptor antagonist that increases norepinephrine release), and after BSTv or mPOA infusion of the more selective α2 autoreceptor antagonist idazoxan. Lastly, noradrenergic input to the BSTv/mPOA was selectively lesioned in nulliparous rats with anti-DBH-saporin to determine if this would facilitate mothering. BSTv yohimbine almost abolished retrieval of pups but did not significantly affect dams' ability to initiate contact, lick, or nurse them. BSTv idazoxan disrupted retrieval somewhat less than yohimbine, but significantly reduced nursing. mPOA idazoxan impaired retrieval more severely than that found after BSTv infusion. Anti-DBH-saporin almost eliminated noradrenergic terminals in the BSTv and reduced them by over 60% in the mPOA, but did not promote maternal responding. It also did not affect females' anxiety-related behavior. Downregulated noradrenergic activity in the BSTv and mPOA is necessary for postpartum maternal behavior in rats, but eliminating this system alone is insufficient to promote maternal behaviors in nulliparous females.

Cooperative behavior of laboratory rats (Rattus norvegicus) in an instrumental task.

Cooperation is a cognitively demanding, complex social behavior, found primarily in primates. Here we investigated mutualism in rats (Rattus Norvegicus), a simple form of cooperation in which two subjects work on operant task, receiving immediate and simultaneous sucrose reward for a joint action. To receive the sucrose reward, familiar pairs of rats were required to nose poke simultaneously. Following 44 training days, we examined the relation of social contact and ultrasonic vocalizations to the rat's cooperative behavior by testing the effects of inserting opaque, wire-mesh, or no partition--between subjects. Cooperative behavior (simultaneous nose-poking): (a) increased gradually during initial training; (b) decreased with the opaque partition (restricting visual, acoustic, and physical communication); (c) increased with a wire mesh partition restricting only physical contact); and (d) increased with the number of 50 kHz USV "happy" calls and the intensity of social interaction. The possibility of studying the development of cooperative behavior in laboratory rats using a simple procedure based on commercially available equipment may prove useful in modeling determinants of social behavior.

Learning and Individual differences in Aggressive Behavior Observed in Rats that Have Lived in Small Mixed Colonies

An experiment was performed to determine the relationship between open field measures (ambulation and defecation) and aggressive behavior in laboratory rats. Learning influences over this relation were considered. Colony-maintained laboratory procedure was not effective to increasethe aggresive behavior of animals when un intruder rat was placed into the colony. In the subjects not exposed to prior attack conditioning the classification variables ambulation and defecation were not enough important to determine or influence the aggression level. Nevertheless, the observed tendency was that the rats with high ambulatory scores were more aggressive than the low ones, and the rats with low defecation scores were more aggressive than the high ones. In the subjects exposed to prior attack oonditioning the Subjects with high ambulation and high defecation scores were the more aggressive. Then, these Subjects learned more quickly than the low ambulation and defecation ones.

Effects of a gentling programme on the behaviour of laboratory rats towards humans

The present study investigated the effects of a gentling programme on the later behaviour of laboratory rats towards humans. For that purpose, 24 female Wistar rats were purchased from a laboratory animal breeding facility at the age of 21 days and allocated, genetically balanced, to an experimental and a control group. The animals were kept under standard laboratory conditions in groups of three. The experimental group was subjected to a gentling programme twice daily for 10 min per cage in the fourth and fifth week of life. This involved gentling and hand-feeding the animals. In addition, the animals were talked to during gentling. At the beginning of the 6th, 8th, 10th and 14th week of life as well as at the age of 6, 6.5 and 9 months the animals of both the experimental and the control group were subjected to tests in order to assess the rats’ behaviour towards humans. In the 14th week of life as well as at the age of 6 months the same test was additionally carried out by a person not familiar to the rats for the purpose of studying the animals’ behaviour towards unfamiliar persons. At each testing point a precisely defined, standardised test procedure was carried out, including among other things, repeated catching of the animals, neck grip, a hand test and a modified open field test involving a human stressor. Evaluation of the results was based on five primary endpoints which defined and summarised the most important parameters of the test procedure for the assessment of “tameness” towards humans. Significantly higher values in the primary endpoints were noted in the experimental group when compared to the control group in the test performed during the sixth week of life. The statistically estimated difference between the experimental and control groups was present until the age of 6 months. This suggested a higher level of “tameness” in the experimental group and a long-term effect of the gentling programme. Contrary to the experimental group, the control group showed a significant increase in tameness over time, which can be attributed to the animals getting used to the repeated tests or an age-related effect. The analysis of the difference between familiar and unfamiliar experimenters showed a borderline significant effect. The experimental and control groups were both slightly tamer with the unfamiliar person. The gentling programme had a beneficial long-term effect on the behaviour of the rats and proved suitable to reduce the laboratory rats’ fear of humans.

Exposure to Urine of Canids and Felids, but not of Herbivores, Induces Defensive Behavior in Laboratory Rats

Predator odors induce defensive behavior in many prey species. For various reasons, studies carried out up to now have been unable to establish whether predator odor recognition is innate or not. Mostly, only particular odors or wild-living (i.e., experienced) test animals have been used in these studies, restricting the conclusiveness of the observations. In the present study, the behavioral effects of exposure to different predator odors on predator odor-naive laboratory male rats were compared with the effects of different nonpredator odors and of a no-odor control stimulus. Results show that exposure to urine of canids and felids, but not of herbivores or conspecifics, induce defensive behaviors. Taken together, the study provides support for the hypothesis that there is an innate recognition of predator odors in laboratory rats.

Social behavior in laboratory rats: Applications for psycho‐neuroethology studies

ABSTRACTThe social behavior in laboratory animals occurs in conspecific groups. In the past two decades, the physiological basis of the social behavior in laboratory rats has been gradually elucidated through various neural approaches. In addition, the relevance of social related behavior for psycho‐neuroethology studies has been extensively proposed. An analysis of social recognition behavior of new conspecifics is a useful approach for the study of memory without aversive alternatives such as fear, pain and anxiety. Furthermore, it is considered that artificial or experimental social isolation can induce altered emotional states in laboratory rats. This article reviews the past findings regarding social behavior and aspects of its expression, and discusses further possibilities for animal models of human neuro‐psychiatric disorders.

Blood glucose dynamics and control of meal initiation: a pattern detection and recognition theory.

A new framework for understanding the control of feeding behavior, with special emphasis on the evolution of hunger, the initiation of feeding, and its dependence on patterns of blood glucose, is the subject of this review. A perspective on the current status and future directions of this search for a more complete understanding of the regulation of feeding behavior in laboratory rats and humans is presented including theoretical and experimental components. First, a historical perspective on the role of blood glucose in the control of feeding is presented. Next, the theoretical approaches that have been applied to the control of feeding and had a strong influence on experimental feeding research are summarized. This is followed by a statement and overview of a current theory that has emerged from studies of the role of transient declines in blood glucose in the control of meal initiation. The current working hypothesis that transient declines in blood glucose are endogenous metabolic patterns that are detected and recognized by the central nervous system and are mapped into meal initiation in rats and are correlated with meal requests in humans are then presented. Then, the experimental studies on meal initiation and its dependence on patterns of blood glucose, first in rats and then in humans, are reviewed in detail. Finally, the future directions of the work, limitations, and the implications for the understanding of the control of feeding behavior and the regulation of energy balance are discussed.

Relation of Fos-IR expression in the pelvic ganglion to sexual behavior in laboratory rats.

The pelvic ganglion (PG) provides both sympathetic and parasympathetic innervation to the genitalia and other pelvic structures. To determine whether neuronal activity; of the PG, as detected by Fos-like immunoreactivity (Fos-IR), is related to sexual stimulation, male and female rats were tested under a variety of conditions. In males, Fos-IR expression in the PG was positively correlated with the amount of both genital and noncontact stimulation. In females, only ejaculation preceded by multiple intromissions induced a significant increase in Fos-IR; multiple intromissions or ejaculation preceded by only 0-1 intromission did not affect Fos-IR. Additional experiments comparing Fos-IR expression, in which some females were allowed to pace their sexual contact and others were not, revealed that ejaculation duration was the key factor in the induction of Fos-IR in female rats. Because the conditions under which Fos-IR expression occurred in females are identical to those required for sperm transport, we suggest that, in the female, sperm transport is regulated in part by autonomic outflow from the PG after copulation. These relations between sexual behavior and measures of PG activity are consistent with the idea that the sexually dimorphic organization of the peripheral nervous system plays a major role in mediating the gender-specific outcome of copulation: ejaculation in the male and sperm transport in the female.

Relation of Fos-IR expression in the pelvic ganglion to sexual behavior in laboratory rats.

Relation of Fos-IR expression in the pelvic ganglion to sexual behavior in laboratory rats.

Regulation of Male Sexual Behavior by Progesterone Receptor, Sexual Experience, and Androgen

Recent studies have demonstrated that physiological doses of progesterone may facilitate the androgen-dependent display of male sexual behavior in laboratory rats and three species of lizard. We used mice with a targeted disruption of the progesterone receptor to investigate whether such interactions exist in male mice and whether they may be modified by sexual experience. We found that naive intact male progesterone receptor knockout (PRKO) mice exhibit reduced mount frequencies compared to wild-type (WT) mice. Also unlike WT mice, sexually experienced PRKO males show profound losses in many measures of sexual behavior following castration. In a second experiment, we tested whether male mice heterozygous for a null mutation at the progesterone receptor locus were responsive to testosterone and progesterone treatment. We found that heterozygous males showed a reduced response to testosterone. The data are consistent with experiments indicating that the progesterone receptor is able to facilitate male-typical sex behaviors in other species and suggest novel mechanisms underlying the interaction of androgens and experience.

A prenatal source for defeminization of female rats is the maternal ovary

Sexual behavior in laboratory rats is influenced by a variety of factors in the perinatal environment. Male rats are masculinized and defeminized in response to circulating testosterone perinatally. Females undergo a process of feminization but in some cases are exposed to testosterone. Previous work has shown that during prenatal development female rats normally undergo a partial masculinization and defeminization of sexual behavior as reflected by altered responsiveness to gonadal hormones in adulthood. In the present study we investigated whether the maternal ovary influences adult females' responsiveness to gonadal hormones. Pregnant rats were ovariectomized on Day 10 of pregnancy and their offspring tested for sexual behavior in adulthood. Following ovariectomy pregnancies were maintained by administration of systemic progesterone. In addition the ovariectomized pregnant rats were given one of three daily treatments (Days 10–21): 0.2 μg estradiol benzoate in sesame oil and 0.1 cc propylene glycol, 5 mg of the aromatase inhibitor 1,4,6-androstatriene-3,17-dione (ATD) in 0.1 cc propylene glycol, or 0.1 cc propylene glycol. A control group was generated from SHAM operated mothers given daily control injections of propylene glycol and sesame oil. Offspring were ovariectomized in adulthood and tested for display of feminine sexual behavior in response to estradiol benzoate and progesterone or estradiol benzoate alone. Masculine sexual behavior was measured in response to testosterone propionate (TP). Feminine sexual behavior was enhanced in offspring from ovariectomized mothers given only progesterone replacement during pregnancy. Offspring from mothers treated with ATD displayed the greatest elevations in feminine sexual behavior. Estradiol treatments of ovariectomized mothers prevented the increase in feminine potential seen in offspring in the other groups. Masculine sexual behavior in response to daily treatment with testosterone propionate did not differ between groups. The results indicated that the maternal ovary was associated with a defeminization to female offspring. It is suggested that normal female rats undergo a reduction in eventual responsiveness to ovarian hormones as a result of exposure to estrogens prenatally; the present study indicates that at least some of these estrogens originate in the maternal ovary.

Differences in maternal behavior of rats and the sociosexual development of the offspring.

This paper describes experiments designed to investigate long-term behavioral consequences for offspring of changes in maternal behavior directed toward them as pups. Specifically, the hypothesis was considered that experimentally induced alterations in maternal behavior would result in general and wide-ranging effects on offspring development, including effects on later social and sexual behavior. The first experiment looked at the effects of changing pup odors on maternal responsiveness toward the pups, and showed that the application of perfume, particularly to the anogenital region, resulted in significant lowering of maternal anogenital licking of pups. Non-pup-directed behavior did not differ between groups. The behavior of those pups that had thus differed in infant experience was then followed in three subsequent experiments. In Experiment 2, social behavior during the juvenile period was investigated, focusing particularly on the expression of social play. The most noticeable difference to emerge in this experiment was that male pups that had been anogenitally perfumed as infants showed much higher levels of social play than male or female pups from other treatment groups. The last two experiments considered adult behavior. Experiment 3 showed that there are no lasting effects of the neonatal treatment on the attractiveness an animal has for its conspecifics. In the final experiment, "masculine" sexual behavior of males (mounts with intromission), and "feminine" sexual behavior of females (i.e., lordosis and proceptive behavior) were investigated. This confirmed previous reports by Moore (1984) (Moore, C. L. (1984). Maternal contributions to the development of masculine sexual behavior in laboratory rats. Dev. Psychobiol., 17:347-363) that those male pups that had received lower rates of anogenital licking as pups showed longer intermount intervals, when tested as adults. The results are discussed in relation to the development of sexually differentiated behavior.

Effects of scheduled food and water deprivation on food intake, water intake and body weight of cage-adapted and cage-naive rats

The first experiment examined the effects of four food-deprivation schedules and four water-deprivation schedules on body weight, food intake and water intake of adult rats over ten days of deprivation and two days of recovery. During food deprivation, water intake was gradually reduced. During water deprivation, daily food intake was initially depressed but eventually returned to ad libitum levels. Consumption of restricted commodities increased over the deprivation phase. Experiment 2 showed that mutual deprivation of food and water are more apparent in rats not previously adapted to the test environment and the final experiment indicated that this was due to the inexperience of cage-naive rats in feeding under novel conditions. The results are evaluated in relation to the environmental factors that may play as great a role as physiological processes in regulating the feeding/drinking behaviour of laboratory rats.

Maternal contributions to the development of masculine sexual behavior in laboratory rats.

Maternal licking was manipulated by lining the nasal passages of rat dams with polyethylene tubing to interfere with their olfactory competence. Olfactory cues from pups elicit maternal licking and handling, particularly of anogenital regions, and dams with olfactory deficits were observed to lick their pups less. Mature male and female offspring of these dams and their controls were gonadectomized, treated with testosterone propionate, and tested for masculine sexual behavior. The male offspring of dams that provided less maternal licking had longer ejaculatory latencies, longer post-ejaculatory intromission latencies, and longer inter-intromission intervals than controls. Female offspring of the intubed dams performed fewer mounts and intromissions, had longer intromission latencies, and longer inter-intromission intervals. It was concluded that stimulation from maternal licking contributes toward the development of a mechanism that underlies the timing of copulatory rate.

Effects of reactivity to dorsal stimulation and social role on aggressive behavior in laboratory rats

Effects of reactivity to dorsal stimulation and social role on aggressive behavior in laboratory rats

Social isolation at weaning: Some effects on two measures of activity

Both the age at which housing conditions are imposed and the type of activity measured are shown to affect the results obtained in studies concerned with the effects of social density on the behavior of laboratory rats. In a review of the effects of population density in the cage environment upon the later activity of laboratory rodents, Archer (1970) notes that many of the studies have produced conflicting results. While some investigations have shown isolates to be less active than grouped animals in a novel test situation (Stern, Winokur, Eisenstein, Taylor, & Sly, 1960; Moyer & Korn, 1965; Archer, 1969), others have shown the reverse to be true (Essman, 1966; Weltman, Sackler, & Sparber, 1966). Syme and Hughes (1972) and Syme, in two studies comparing the activity of isolated and grouped rats, suggested several reasons for these discrepancies. Firstly, cage size of isolated animals was shown to affect activity in the open field, and secondly, it was demonstrated that rats and mice should be considered separately since activity differences arising from grouped and isolated housing conditions are opposite for the two species within 1 day of weaning. There are, however, a number of other contributing variables, two of which arc investigated in this study. It is possible that the age at which housing conditions arc introduced is important. Bronfenbrenner (1968) suggests that the effects of stimulus deprivation are negatively related to the age at which such deprivation occurs. The present experiment was designed primarily to investigate the effect of imposing different housing conditions at weaning rather than at some later time. In contrast to Archer (1969), who isolated female rats at 40 days of age and compared their activity with that of grouped animals 24 weeks later, this study used female rats isolated at weaning and tested them after the same period in comparison with control-grouped and crowded animals. Adrenal weights, as a supplementary index of social stress (Schnurer, 1963; Barnett, 1964), were obtained after 3 and 6 months. Two measures of activity are used. Locomotor activity was observed in an open field, while nonspecific general activity was measured on an activity platform. This provides a test of the prevalent assumption (Baumeister, Hawkins, & Cromwell, 1964) that the different methods can be regarded as equivalent when comparisons of activity studies arc made.

The behaviour of laboratory rats in a social learning situation

Seven experiments are described which used laboratory rats in a social learning situation. ‘Divisions of labour’ where one animal did most of the ‘work’, developed under a variety of controlled conditions i.e. in groups given different individual training procedures, in groups run in different pieces of apparatus, in those run at ‘survival’ level, in groups which remained in the apparatus until they were no longer hungry, and in groups trained in groups under a number of different experimental procedures. To this extent the observed performance differences may be considered to be a ‘genuine’ phenomenon of experimental ‘social’ organisation. On the other hand, groups differed considerably in their overall performance rates, in the variety of ‘solutions’ which were observed whereby ‘worker’ rats obtained a proportion of the food produced, and on a number of general observations relating to competitive and ‘sexual’ behaviours. Problems are raised which have application for studies of experimental social behaviour and organisation, including that of attempting to assess the ‘conceptual status’ of the main performance measures which were used to compare individual animals' in a ‘social’ situation using a much used experimental psychological technique–namely an operant conditioning task.