Recombinant congenic strains of mice from B10.D2 and DBA/2: Their contribution to behavior genetic research and application to audiogenic seizures

Recombinant congenic strains (RCS) represent a series of related strains, each of which carries a small fraction of the genome of one strain (donor strain) on the genetic background of another strain (background strain). Recombinant inbred strains (RIS) are commonly used to identify major gene segregation and linkage and associations between behavior and quantitative trait loci, whereas recombinant congenic strains (RCS) open other complementary leads. The variability in the reactivity of RCS to a trait is thus the expression of few minor-effect genes originating from the donor strain, because the probability that major genes are present in any one RCS is low. Unlike RIS in which minor-effect genes are often masked by major genes, RCS enable the effects of minor genes to be studied. With our method, for a given trait, an estimate can be made of the gene strength distribution as well as an estimate of the minimal number of genes involved having a certain strength.This study was supported by the Centre National de la Recherche Scientifique (URA 1924 and CSEAL-UPS 44, CNRS), Université René-Descartes, Paris V UFR Biomédicale, and the Fondation pour la Recherche Médicale.     

Factors influencing active avoidance behavior in rats with ventromedial hypothalamic lesions

Ventromedial hypothalamic lesioned rats maintained at preoperative body weight received an equal number of shocks while emitting significantly fewer responses than controls in a lever-pressing free-operant avoidance paradigm, and performed as well as unoperated animals in lever-pressing and shuttle box (both 1- and 2-way) discriminated avoidance tasks. The failure of VMH lesions to facilitate performance in the 2-way avoidance paradigm was probably the result of a ceiling effect. With the exception of the simple one-way avoidance task, obese lesioned rats were markedly impaired in the acquisition of all active avoidance behavior, but escape behavior was not affected. When tested in a free-operant paradigm, the avoidance performance of well trained lesioned animals varied inversely with body weight. As obese rats displayed lower flinch thresholds to shock than controls and similar levels of activity and responding as lean lesioned animals, it was concluded that their impaired avoidance behavior was not due to changes in sensitivity or mobility. The possible relation to other VMH lesion- and/or obesity-induced deficits is discussed.     

Heart Rate Reactivity and Type A Behavior as Modifiers of Physiological Response to Active and Passive Coping

We examined the long term predictivity of heart rate reactivity (HRR) and its relation to cardiovascular and biochemical activity during rest and during tasks requiring active and passive coping. HRR was determined in 28 young men by measuring peak heart rate change to cold pressor one year after performing tasks eliciting active and passive coping. Heart rate change to cold pressor was significantly correlated with change to active coping (r= .65, p<.01) and to passive coping (r= .53, p<.01). Responses to the tasks were equivalent for Type A and B subjects. On the other hand, high HRRs were significantly more reactive than low HRRs with the effect being most apparent during active coping. HRR appeared to be a trait stable over one year which predicted enhanced cardiac, neuroendocrine, and neuromuscular response.     

Open-field behavior and the peripheral sympathetic nervous system in the MR/N and MNR/N rat strains

The Maudsley Reactive (MR) and Maudsley Non-Reactive (MNR) strains of rats, respectively selected by P. L. Broadhurst for high and low open-field defecation (OFD), were acquired by the National Institutes of Health in 1963 at the 21st generation of inbreeding and have been inbred as the MR/N and MNR/N strains at that location for more than 40 generations. The present experiment shows that, despite the lack of deliberate selection for more than 40 generations, the strains still differ predictably in OFD. Strain differences in open-field activity, originally found to be inversely associated with those in OFD, have also been preserved. The existence of an association between the peripheral sympathetic system and OFD originally established in the Har derivation of the Maudsley strains was also confirmed in the MR/N and MNR/N strains: MR/N male rats, with the relatively higher levels of OFD, exhibited lower concentrations of norepinephrine (NE) in spleen and descending colon than MNR/N rats. The pattern of biochemical and morphological findings obtained in this study and previous data indicate that the MNR/N and the MNR/Har strains are both derived from the British stocks of this strain carrying the agouti allele (AA). A distinction should be made between these strains and the MNRA/Har strain, which carries the nonagouti allele (aa) and which has been genetically isolated from the Nonreactive strains bearing the agouti allele since early in the selection experiment.Supported by Grant GM 28874 from the National Institute of General Medical Sciences.     

The maternal pheromone of the rat as an innate stimulus for pre-weanling young

We undertook to determine whether previous exposure in the nest is necessary to establish the attractiveness of the maternal pheromone or whether that attractiveness is innately based. In Experiment 1 we showed that the pheromone is a prepotent stimulus insofar as it is approached in preference to a different but equally familiar odor. Experiment 2 demonstrated that when pups are denied previous exposure to the pheromone they nonetheless approach the pheromone preferentially in a choice test involving a pheromone-emitting and a non-pheromone-emitting female. And finally, in Experiment 3, we again used pups that had been isolated from the pheromone. Here, however, the choice was between a pheromone-emitting female and a female which, while non-pheromone-emitting, carried a thoroughly familiar nest odor. The pups decisively chose the pheromone-emitting female. We conclude that pheromonal attractiveness is innately based and suggest that the pheromone itself may have been selected as a signal during the course of evolution.     

Involvement of 5-HT2 receptors in the LSD- and L-5-HTP-induced suppression of lordotic behavior in the female rat

Summary Copulatory behavior in the ovariectomized rat, the lordotic response (L. R.), was induced by estrogen followed by progesterone. L. R. is inhibited by lysergic acid diethylamide (LSD) (0.05 mg/kg) and by Levo-5-hydroxytryptophan (L-5-HTP) (2.5 mg/kg). The effects of the putative 5-HT antagonists lisuride, metergoline, methysergide, mianserin, cinanserin, cyproheptadine, pirenperone and altanserin on the LSD-induced inhibition of L. R. were tested. Lisuride, metergoline, methysergide and mianserin were found to have no LSD-blocking effect. In contrast, cinanserin, cyproheptadine and pirenperone acted antagonistically to LSD, within a critical dose range. The selective 5-hydroxytryptamine₂ (5-HT₂) receptor antagonist altanserin effectively prevented the LSD-induced inhibition of L. R., and the doses required (0.05–0.20 mg/kg) indicated a comparatively high antagonistic potency. In addition altanserin (0.2 mg/kg) effectively prevented the lordosis inhibitory effect induced by L-5-HTP (2.5 mg/kg), after pretreatment with pargyline and RO4-4602. It is suggested that the suppression of copulatory behavior caused by LSD and L-5-HTP is mediated by 5-HT₂ receptors.     

Effects of D2-dopaminergic receptor stimulation on male rat sexual behavior

Summary The effects of selective D₂-dopaminergic receptor stimulation with LY163502 on male rat copulatory behavior were evaluated. LY163502 (25 ng/kg to 25g/kg s. c.) produced increases in the percentage of sexually inactive rats displaying mounting behavior and ejaculating during the test period. Within this same dose range, LY163502 administration induced an increase in the percentage of non-ejaculator rats that were capable of ejaculation. These findings are viewed as evidence that LY163502 can initiate sexual behavior and lower the threshold for ejaculation. The effects of LY163502 were further evaluated in rats that were capable of ejaculation during the test period. LY163502 (25 ng/kg to 25g/kg s. c. or p. o.) induced significant reductions in ejaculatory latency. These effects were blocked by prior treatment with centrally active dopaminergic antagonists, RO 22-1319 and sulpiride, but not with a peripherally active antagonist, domperidone.LY163502 administration was also found to inhibit sexual behavior in low doses of 25 pg/kg –10 ng/kg s. c. and in a much larger dose of 25 mg/kg s. c. These inhibitory effects are viewed as behavioral manifestations of selective dopaminergic autoreceptor activation with low doses and as the disruption of sexual behavior by induction of intense stereotypic behavior with high doses.     

Stretched attend posture,a non-social form of ambivalence,is sensitive to a conflict-reducing drug action

Based upon the ethological element stretched attend to a conspecific, which reflects ambivalence between approach and avoidance in a social context, a simple, non-social behavioral method for studying conflict behavior in mice was investigated. Thus, stretched attend posture (SAP) and other behavioral acts were measured in untreated or drug-treated mice which were individually placed on a perforated platform previously rubbed with foreign male urine and boluses. In naive, untreated mice, the occurrence of SAP was partly housing- and lighting-dependent. After repeated exposure to the test situation, untreated mice showed less SAP, whereas static behavior (immobility and activity at rest) was increased. After single oral treatment with diazepam, clobazam or phenobarbital, SAP was reduced, whereas static behavior or going forwards in SAP was increased. Chlorpromazine and imipramine did not influence SAP. In naive mice, single IP injection of pentylenetetrazol did not significantly increase SAP. The similarity in the behavioral response between experienced, untreated mice and naive animals treated with diazepam, clobazam, or phenobarbital suggests that drug-treated mice behaved as if they were already familiar with the test situation. The latter drug-induced changes are consistent with data obtained in animal models which are based upon the measurement of behavioral inhibition. Under the present test conditions, pentylenetetrazol did not show anxiogenic properties. Nevertheless, the SAP test, based primarily on the measurement of the ambivalence element, offers a simple procedure for examining the conflict-reducing properties of drugs, dispensing with the need of noxious stimuli or prior training.Some of these results were presented at the 15th Annual USGEB/USSBE Meeting in Fribourg, Switzerland (17–18 March 1983) and, published in abstract form in Experientia (1983) 39(6):681–682     

Dietary Aspects to Incorporate in the Creation of a Mobile Image-Based Dietary Assessment Tool to Manage and Improve Diabetes

Diabetes is the seventh leading cause of death in United States. Dietary intake and behaviors are essential components of diabetes management. Growing evidence suggests dietary components beyond carbohydrates may critically impact glycemic control. Assessment tools on mobile platforms have the ability to capture multiple aspects of dietary behavior in real-time throughout the day to inform and improve diabetes management and insulin dosing. The objective of this narrative review was to summarize evidence related to dietary behaviors and composition to inform a mobile image-based dietary assessment tool for managing glycemic control of both diabetes types (type 1 and type 2 diabetes). This review investigated the following topics amongst those with diabetes: (1) the role of time of eating occasion on indicators of glycemic control; and (2) the role of macronutrient composition of meals on indicators of glycemic control. A search for articles published after 2000 was completed in PubMed with the following sets of keywords “diabetes/diabetes management/diabetes prevention/diabetes risk”, “dietary behavior/eating patterns/temporal/meal timing/meal frequency”, and “macronutrient composition/glycemic index”. Results showed eating behaviors and meal macronutrient composition may affect glycemic control. Specifically, breakfast skipping, late eating and frequent meal consumption might be associated with poor glycemic control while macronutrient composition and order of the meal could also affect glycemic control. These factors should be considered in designing a dietary assessment tool, which may optimize diabetes management to reduce the burden of this disease.