Biomedical subjects

P Mormède

Publications and source records attributed to P Mormède.

At least 19 recordsLinked to original sources

PubMed2001

Differential sensitivities to the lethal, but not the neurotoxic, effects of p-chloroamphetamine in inbred rat strains.

The Lewis, Fischer 344, Brown Norway, Spontaneously Hypertensive, and Wistar-Kyoto inbred rat strains were, respectively, compared for the lethal and neurotoxic effects of acute p-chloroamphetamine (PCA, 2.5-10 mg/kg i.p.). The lethal properties of the amphetamine were recorded within 24 h after its administration whereas neurotoxicity (as assessed by frontocortical 5-hydroxytryptamine (5-HT) reuptake and 5-HT transporter binding assays) was analyzed 1 week after PCA administration. Preliminary experiments indicated that neither the rapid hyperlocomotor and/or the hypoexploratory effect of PCA nor the in vitro potency of PCA to inhibit frontocortical [(3)H]5-HT reuptake varied between strains. On the other hand, strain differences were observed with respect to the rapid fatal effects of the 5 and 10 mg/kg doses of PCA administration. Lastly, frontocortical [(3)H]5-HT reuptake and [(3)H]citalopram binding at 5-HT transporters diminished in a dose-dependent, but strain-independent, manner 1 week after the acute injection of PCA. This study reveals an independency between the mechanisms underlying the fatal effects of PCA on the one hand, and the long-term damaging effects of PCA on serotonergic neurons on the other hand.

Animals↗

PubMed2001

Neuroendocrine consequences of very early weaning in swine.

An experiment was conducted to investigate the consequences of very early weaning of piglets on neuroendocrine variables and growth. Sixty piglets from eight litters were either weaned on Postnatal Day 6 (early weaning, or EW piglets) or left with their dam until normal weaning at Day 28 (control piglets, or C). At Days 5, 7, 11, 14, and 19, urine was collected between 7:00 and 8:00 a.m. for the measurement of catecholamines, glucocorticoids, and creatinine. Compared with C, EW piglets displayed a transient increase in urinary cortisol on the day following separation from their dam (Day 7) (P<.05). Urinary norepinephrine (NE) was three times lower in EW compared to C piglets from Day 7 until Day 14 (P<.01) but there was no difference between the two groups on Day 19. Urinary epinephrine (EPI) did not differ between C and EW piglets on the day after weaning. Thereafter, EW piglets displayed a three times drop in urinary EPI as compared to C piglets until the end of the period (P<.01). Weaning induced an immediate reduction in food intake and growth rate and at Day 28, the body weight of EW piglets was 1.60 kg lower than that of C piglets (P<.0001). In conclusion, weaning of 6-day-old piglets results in a marked and prolonged suppression of the release of catecholamines. This result likely reflects physiological responses to insufficient energy intake after weaning, as reflected also by changes in thermoregulatory behavior. The transient increase in cortisol excretion in weanlings may be caused by both emotional distress and acute food deprivation.

Aging↗

PubMed2001

Strain-dependent effects of diazepam and the 5-HT2B/2C receptor antagonist SB 206553 in spontaneously hypertensive and Lewis rats tested in the elevated plus-maze.

The 5-HT2B/2C receptor antagonist SB 206553 exerts anxiolytic effects in rat models of anxiety. However, these effects have been reported for standard rat strains, thus raising the issue of SB 206553 effects in rat strains displaying different levels of anxiety. Herein, the effects of SB 206553 in a 5-min elevated plus-maze test of anxiety were compared to those of the reference anxiolytic, diazepam, in two rat strains respectively displaying high (Lewis rats) and low (spontaneously hypertensive rats, SHR) anxiety. Diazepam (0.37, 0.75, or 1.5 mg/kg; 30 min before testing) increased in a dose-dependent manner the behavioral measures in SHR, but not in Lewis rats. On the other hand, SB 206553 (1.25, 2.5, or 5 mg/kg; 30 min before testing) failed to alter the anxiety parameters in both strains, whereas it increased closed arm entries in Lewis rats, suggesting that it elicited hyperactivity in the latter strain. Accordingly, the hypolocomotor effect of the nonselective 5-HT2B/2C receptor agonist m-chlorophenylpiperazine (1.5 mg/kg ip 20 min before a 15-min exposure to an activity cage) was prevented by the 1.25 and 2.5 mg/kg doses of SB 206553 in Lewis rats and SHR, respectively. Compared with SHR, Lewis rats may display a lower response to benzodiazepine-mediated effects and a more efficient control of locomotor activity by 5-HT2B/2C receptors.

Animals↗

PubMed2001

Sex and strain differences in ethanol drinking: effects of gonadectomy.

BACKGROUND: Alcohol drinking behavior in rats is known to be sexually dimorphic and strain-dependent. METHODS: To test whether the gonadal steroid milieu exerts activational effects on ethanol intake and can modulate individual sensitivity toward alcohol use and misuse, we examined the effects of gonadectomy on oral self-administration (OSA) of ethanol in male and female rats from different strains. After castration, animals were given continuous free choice between water and ethanol solutions. The ethanol concentration was progressively increased from 2% to 10% and maintained at 6% (the preferred concentration) for 24 days. Ethanol solutions were then withdrawn for 9 days. During the second phase of free-choice drinking, the ethanol concentration was gradually increased every 4 days by the following amounts, in order as listed: 6%, 12%, and 24%. RESULTS: Our results confirm both gender and strain differences in ethanol drinking: females exhibited higher ethanol intake than males, and the WKHA strain drank more than the WKY and SHR strains. However, except for a small decrease in ethanol drinking during the acquisition of ethanol OSA in males after castration, no clear-cut difference was found between gonadectomized and sham-operated animals during the maintenance of ethanol OSA behavior. CONCLUSIONS: These data suggest that gender and strain differences observed are insensitive to gonadal steroids during adulthood, and that different sensitivities to the effect of gonadal steroids do not explain the sex x strain interaction observed in ethanol drinking.

Alcohol Drinking↗

PubMed2000

Hippocampal and striatal [(3)H]5-HT reuptake under acute stressors in two rat strains differing for their emotivity.

Spontaneously hypertensive rats and Lewis rats differ in their anxiety levels and in their serotonergic and corticotropic responses to stress. Since the 5-HT transporter plays a key role in 5-HT neurotransmission, we have analyzed whether hippocampal and/or striatal [(3)H]5-HT reuptake kinetics are altered by stress in a strain-dependent manner. It was found that forced swimming, treadmill running, or restraint for 30 min affected neither hippocampal nor striatal [(3)H]5-HT reuptake K(m) and V(max) values in the two rat strains. This study, which is the first to examine the impact of acute stress on [(3)H]5-HT reuptake with respect to the nature of the stressor, the brain region analyzed, and the rat strain, could reinforce the hypothesis that extracellular 5-HT levels during stress are representative of 5-HT release.

Animals↗

PubMed2000

Strain-dependent neurochemical and neuroendocrine effects of desipramine, but not fluoxetine or imipramine, in spontaneously hypertensive and Wistar-Kyoto rats.

Spontaneously Hypertensive rats (SHRs) and Wistar-Kyoto (WKY) rats differ in their emotional responses to stress and antidepressant administration. We have analysed different neurochemical and psychoneuroendocrine responses to repeated pretreatments with fluoxetine, imipramine or desipramine (10 mg/kg p.o. daily for 4 weeks) in SHRs and WKY rats exposed to a daily 2-h restraint episode for the last 5 days of antidepressant administration. Following a 24-h wash-out period, WKY rats displayed higher plasma antidepressant and antidepressant metabolite levels than SHRs. Fluoxetine pretreatment decreased [(3)H]citalopram binding at midbrain serotonin (5-HT) transporters, whereas tricyclic and/or fluoxetine decreased [(3)H]ketanserin binding at cortical 5-HT(2A) receptors, [(3)H]CGP-12177 binding at cortical ss-adrenoceptors, and [(3)H]nisoxetine binding at midbrain noradrenaline (NA) transporters in both strains. None of the antidepressants affected [(3)H]8-hydroxy-2-(di-N-propylamino)tetralin binding at hippocampal 5-HT(1A) receptors. In WKY rats, repeated restraint triggered a desipramine-sensitive 140% increase in hypothalamus [(3)H]nisoxetine binding; moreover, plasma adrenocorticotropin-releasing hormone responses to a 5-min open field test were amplified by prior repeated restraint in both strains, but desipramine prevented such an amplification in WKY rats only. However, neither elevated plus-maze nor open field behaviors of SHRs and WKY rats were affected by desipramine pretreatment. Thus, the SHR and WKY rat strains may prove useful in understanding how genetic differences in noradrenergic responses to repeated stress and desipramine treatment impact on adaptive processes.

Adrenocorticotropic Hormone↗

PubMed2000

Serotonin reuptake inhibition by citalopram in rat strains differing for their emotionality.

Acute administration of the selective serotonin (5-HT) reuptake inhibitor (SSRI), citalopram (1-10 mg/kg, i.p. 1 h before an elevated plus-maze test), to Spontaneously Hypertensive rats (SHRs), Lewis (LEW) rats, and Wistar-Kyoto (WKY) rats, i.e., rat strains differing for their emotionality, promoted anxiety, and/or hypoactivity, except in WKY rats. In the three strains, such a pretreatment increased central 5-HT levels and/or decreased 5-hydroxyindoleacetic acid levels. Hippocampal, but not midbrain or striatal, [3H]citalopram binding at 5-HT transporters was lower in WKY rats than in SHRs. However, neither [3H]5-HT reuptake kinetics nor the potencies of citalopram (1-1000 nM) to inhibit [3H]5-HT reuptake into hippocampal and striatal synaptosomes differed between strains. This was confirmed in vivo by means of microdialysis in the hippocampus of freely moving rats. Thus, although LEW rats displayed a 3-4 fold higher baseline level of extracellular 5-HT in the hippocampus, compared with SHRs and WKY rats, local perfusion with 1 microM citalopram promoted relative increases in extracellular 5-HT levels over baseline that were similar in all strains. Lastly, acute i.p. administration of 3.3 mg/kg citalopram (1 h beforehand) decreased to similar extents [3H]5-HT reuptake into hippocampal synaptosomes from SHRs and WKY rats. This study indicates that genetic differences in the behavioural responses to SSRIs may involve 5-HT transporter-independent mechanisms.

Animals↗

PubMed2000

Is the mineralocorticoid receptor in Brown Norway rats constitutively active?

In a previous study using corticosterone treatment of adrenalectomized rats, we hypothesized that mineralocorticoid receptor (MR)-related mechanisms are constitutively active and that glucocorticoid receptor (GR)-mediated mechanisms are more efficient in Brown Norway rats compared to Fischer 344 (F344) rats. In order to discriminate the mineralocorticoid from the glucocorticoid actions exerted by corticosterone, F344 and Brown Norway adrenalectomized rats were treated with increasing doses (1, 5 and 25 microg/ml of drinking water) of deoxycorticosterone (DOC, MR-specific ligand) or RU 28362 (GR-specific ligand). These rats were compared with long-term adrenalectomized (ADX) untreated rats and sham-ADX rats. This study confirms our previous results, notably the lack of effect of ADX on body weight and fluid intake in Brown Norway rats. Moreover, DOC treatment had no effect in Brown Norway rats whereas the higher dose restored fluid intake of the F344 ADX group to sham values. These results support the hypothesis of a constitutive activation of the MR and therefore the insensitivity of this receptor to its ligand in Brown Norway rats. Alternatively, RU 28362 treatment induced greater weight loss, decrease in food intake, anxiolysis, thymus involution, and decrease in plasma transcortin concentration and pituitary corticosteroid receptor densities in Brown Norway rats than in F344 rats, which is consistent with greater efficiency of GR mechanisms in Brown Norway rats than in F344 rats. Therefore, these strains are of great utility to disentangle MR and GR effects on complex phenotypes.

Adrenalectomy↗

PubMed2000

Effects of cocaine-induced sensitization on ethanol drinking: sex and strain differences.

Sensitization induced by repeated drug exposure has been proposed to increase 'wanting' the drug and to facilitate the transition from moderate to excessive drug intake. The present study examined the effects of cocaine-induced sensitization on ethanol-drinking behavior in male and female rats from different strains. In experiment 1, rats were pretreated with six injections of saline or cocaine (10 mg/kg, i.p.), spaced by 3-day intervals, and were subsequently allowed access to ethanol intake in an unrestricted free-choice procedure. In experiment 2, rats had acquired ethanol-drinking behavior and were exposed to the sensitizing treatment described previously or were left undisturbed. Subsequently, all animals again had access to ethanol. Whatever the sex and strain concerned, sensitized and control animals did not differ in either the acquisition or the maintenance of ethanol-drinking behavior, suggesting that cocaine-induced behavioral sensitization does not modify ethanol intake. The present results also confirm the sex- and strain-dependent character of alcohol intake and of the 'alcohol deprivation effect'.

Animals↗

PubMed2000

Assessment of hypothalamic-pituitary-adrenal axis and sympathetic nervous system activity in pregnant sows through the measurement of glucocorticoids and catecholamines in urine.

We validated the use of urine to monitor changes in the activity of both the hypothalamic-pituitary-adrenal (HPA) axis and the sympathetic nervous system (SNS) in swine. Ten pregnant sows were fitted with venous catheters 3 wk after mating. In the early (wk 6), middle (wk 9), and late (wk 14) stages of gestation, blood and urine were collected over 24 h to monitor diurnal changes in plasma cortisol, urinary cortisol, and urinary catecholamines (norepinephrine [NE] and epinephrine [EPI]). Dexamethasone suppression tests (DST) and ovine corticotropin-releasing hormone (CRH) challenge tests were also performed at each stage of gestation. All plasma and urinary values changed markedly around the clock. Diurnal variations of urinary cortisol were comparable to those in plasma, with a late nocturnal peak and a trough occurring in the evening. During the dark period, urinary catecholamines were lower than during the light period. Norepinephrine increased sharply after lights came on and peaked after meal time. Epinephrine began to rise at the end of the dark period and peaked just before meal time. Average plasma cortisol increased with the stage of gestation, due to higher levels during daylight hours. Dexamethasone at 2000 (20 microg/kg i.v.) decreased plasma cortisol at 0830 and nocturnal cortisol excretion. The magnitude of the decrease in plasma ACTH and urinary cortisol after DST was lower in late than in early and midgestation, indicating increased feedback resistance at that stage. The CRH (1 microg/kg i.v.) increased plasma and urinary cortisol. Peak levels occurred 30 min and 2 to 3 h after the injection, respectively. Catecholamines and cortisol in urine produced during the night (2000 to 0800) and the early morning (0400 to 0800 and 0800 to 0900) were highly correlated with their 24-h excretion rate. These results indicate that it is possible to monitor changes in the HPA axis and SNS activity through urinary measurements in pigs.

Adrenocorticotropic Hormone↗

PubMed1999

Strain and sex differences in the locomotor response and behavioral sensitization to cocaine in hyperactive rats.

Individual variability in the behavioral responsiveness to psychostimulant drugs is due, in part, to genetic factors. The present study investigated the effects of acute and repeated administrations of cocaine (0, 5, 10 or 20 mg/kg, i.p.) on locomotor activity in male and female rats from genetically distinct strains often used as a model of human childhood hyperactivity/attentional deficit disorder: Wistar Kyoto Hyperactive (WKHA) rats, Spontaneous Hypertensive rats (SHR) and their control Wistar Kyoto (WKY). The results, expressed as percent change in locomotor activity relative to respective control groups, showed that cocaine elicits a dose-dependent hyperactivity in all strains and revealed neither strain nor sex differences in acute sensitivity to moderate doses of the drug. Nevertheless, across repeated administrations, strain and sex differences appeared: WKHA rats displayed a moderate extent of sensitization to psychomotor stimulant effects of cocaine and female rats showed more robust sensitization than males, whatever the strain. These findings support the genotype-dependence in the development of behavioral sensitization to cocaine and confirm the robustness of the sexual dimorphism across different inbred rat strains. Interestingly, the present results demonstrate that sensitization to psychostimulant drugs occurs in genetically hyperactive strains as well as in their normoactive control strain.

Animals↗

PubMed1999

GR 127935 reduces basal locomotor activity and prevents RU 24969-, but not D-amphetamine-induced hyperlocomotion, in the Wistar-Kyoto hyperactive (WKHA) rat.

The hyperlocomotor effect of the serotonin (5-HT)1A,B receptor agonist 5-methoxy-3-(1,2,3,6-tetrahydro-4-pyridinyl)-1H-indole (RU 24969) has been repeatedly reported. However, 5-HT1A receptors, 5-HT1B receptors (or both) have been claimed to mediate this effect of RU 24969. These contradictory data possibly arise from protocol differences, especially those related to animal species, drugs, and activity assessment. Herein, the influence of a pretreatment with the selective 5-HT1B,D receptor antagonist N-[4-methoxy3-(4-methyl-1-piperazinyl)phenyl]-2'-methyl-4'-(5me thyl-1,2,4-oxadiozol-3-yl)-biphenyl-4-carboxamide (GR 127935; 1, 3.3 and 10 mg/kg IP) on the hyperlocomotor effect of a 5 mg/kg (IP) dose of RU 24969 was studied in Wistar-Kyoto Hyperactive (WKHA) rats. In a first series of experiments, it was confirmed that RU 24969 (2.5 and 5 mg/kg), administered 10 min after the onset of activity recordings, increases locomotion dose-dependently (cage crossings). In a second series of experiments, administration of GR 127935 10 min after the onset of activity recordings promoted a dose-dependent decrease in basal activity (and rearings) and prevented (3.3 and 10 mg/kg) RU 24969-elicited locomotor activity. On the other hand, GR 127935 was ineffective against RU 24969-induced inhibition of rearings. Lastly, it was observed that 3.3 mg/kg GR 127935 did not affect the number of cage crossings and rearings displayed by rats administered 1.5 mg/kg D-amphetamine. This study shows that 5-HT1B receptors play a major role in the hyperlocomotor effect of RU 24969, at least under our experimental setting. Whether these receptors also play a tonic role in the high locomotor activity displayed by WKHA rats remains to be determined.

Animals↗

PubMed1999

Characterization of mineralocorticoid and glucocorticoid receptors in pigs: comparison of Meishan and Large White breeds.

Corticosteroids receptors were characterized and compared in central and peripheral tissues of two pig breeds, the Meishan (MS) and the Large White (LW) pigs, that display differences in the basal activity and stress-induced reactivity of the hypothalamic-pituitary-adrenal (HPA) axis. In vitro kinetic experiments on kidney and liver cytosols from adrenalectomized pigs allowed to identify two distinct corticosteroid receptors referred to as mineralocorticoid (MR) and glucocorticoid (GR) receptors. The binding specificities were determined for kidney and hippocampal MR and for liver and hippocampal GR. In hippocampus and peripheral tissues, cortisol showed a greater affinity for MR than for GR. As already described in the dog, mouse and human, dexamethasone and progesterone display a moderate affinity for MR. Putative differences in corticosteroid receptors binding capacities and affinities were investigated by saturation binding studies in specific regions implicated in the regulation of HPA axis (hippocampus and pituitary). The MS pigs evidenced higher densities of hippocampal MR, while LW pigs had higher densities of pituitary GR. Thus, this study suggests that a difference in the MR/GR balance in hippocampus and pituitary could be implicated in the different HPA activity between MS and LW pigs.

Aldosterone↗

PubMed1999

Effects of repeated fluoxetine on anxiety-related behaviours, central serotonergic systems, and the corticotropic axis axis in SHR and WKY rats.

In keeping with the anxiolytic property of selective serotonin reuptake inhibitors (SSRIs) in humans, we have examined in the spontaneously hypertensive rat (SHR) and the Wistar-Kyoto (WKY) rat, which display low and high anxiety, respectively, some psychoneuroendocrine effects of a repeated treatment with the SSRI fluoxetine (5 or 10 mg/kg daily, for 3 weeks). Two days after the last injection, plasma levels of fluoxetine were not detectable whereas those of its metabolite, norfluoxetine, were present to similar extents in both strains. By means of the elevated plus-maze test (29-30 h after the 13th administration of fluoxetine) and an open field test (48 h after the last injection of fluoxetine), it was observed that fluoxetine pretreatment did not yield anxiolysis; hence, some, but not all, behaviours were indicative of anxiety and hypolocomotion (as assessed through principal component analyses and acute diazepam studies). In both strains, the 10 mg/kg dose of fluoxetine decreased hypothalamus 5-HT and 5-HIAA levels, and reduced midbrain and/or hippocampus [3H]citalopram binding at 5-HT transporters, but did not affect [3H]8-hydroxy-2-(di-N-propylamino)tetralin binding at hippocampal 5-HT1A receptors. However, the fluoxetine-elicited reduction in hippocampal 5-HT transporter binding was much more important in WKY than in SHR rats, this strain-dependent effect being associated in WKY rats with a reduction in cortical [3H]ketanserin binding at 5-HT2A receptors. Lastly, in WKY rats, repeated fluoxetine administration increased adrenal weights and the plasma corticosterone response to open field exposure, but did not affect the binding capacities of hippocampal mineralocorticoid and glucocorticoid receptors. These data show that key psychoneuroendocrine responses to repeated fluoxetine administration may be strain-dependent, and that repeated fluoxetine administration does not yield anxiolysis, as assessed by two standard tests of emotivity.

Animals↗

PubMed1999

Behavioral, neuroendocrine and serotonergic consequences of single social defeat and repeated fluoxetine pretreatment in the Lewis rat strain.

We have analysed some behavioral, neuroendocrine and serotonergic consequences of a single (30-min) social defeat followed by 14-18 h of sensory contact with the aggressor, in Lewis rats, an inbred strain highly sensitive to chronic social stressors [Berton O. et al. (1998) Neuroscience 82, 147-159]. In addition, we have investigated how the aforementioned consequences are affected by pretreatment with the selective serotonin reuptake inhibitor, fluoxetine (7.5 mg/kg/day for 21 days). A single social defeat triggered hypophagia and body weight loss, and increased anxiety in the elevated plus-maze. It did not affect baseline plasma adrenocorticotropic hormone levels and renin activity, but decreased plasma corticosterone levels. On the other hand, the responses of the latter variables to subsequent acute forced swim stress were blunted (corticosterone) or amplified (adrenocorticotropic hormone, renin activity) by prior defeat. The density of hippocampal serotonin transporters, but not that of hippocampal serotonin-1A and cortical serotonin-2A receptors, was decreased by a single social defeat; in addition, neither tryptophan availability and serotonin synthesis/metabolism, nor serotonin-1A autoreceptor-mediated functions (inhibition of serotonin synthesis, hyperphagia) were affected. Fluoxetine pretreatment diminished social defeat-induced hypophagia, body weight loss and anxiety without affecting these variables in control animals. This pretreatment increased plasma corticosterone levels in resting and acutely stressed rats, but abolished social defeat-elicited corticosterone hyporesponsiveness to acute forced swim stress. Except for a decrease in midbrain serotonin transporter density, fluoxetine did not affect the other serotonergic indices analysed herein, i.e. serotonin-1A and serotonin-2A receptor densities, serotonin synthesis/metabolism. A single social defeat in Lewis rats produces behavioral and endocrine alterations that may model some aspects of human anxiety disorders. In this paradigm, prior fluoxetine treatment is endowed with adaptive behavioral, and possibly neuroendocrine, effects without affecting the key elements of central serotonergic systems analysed herein.

8-Hydroxy-2-(di-n-propylamino)tetralin↗

PubMed1999

Behavior and pituitary-adrenal function in large white and Meishan pigs.

Six-wk-old piglets of both sexes from European Large White (LW, n = 36) and Chinese Meishan (MS, n = 24) breeds were individually exposed to a novel environment, a stressful stimulation. Behavioral and pituitary-adrenal reactivity were investigated. When compared with LW, MS pigs displayed low locomotion (18.5 +/- 2.2 vs. 41.0 +/- 3.8 squares crossed/10 min; P < 0.0001), and defecation scores (0.58 +/- 0.15 vs. 4.86 +/- 0.37 fecal boli; P < 0.0001). Basal concentrations of cortisol were higher in MS (96.1 +/- 1.1 vs. 44.9 +/- 1.1 ng/ml; P < 0.0001), although no differences between breeds were found in basal concentrations of adrenocorticotropic hormone (ACTH). In response to novel environment exposure, the ACTH increase was greater in LW than in MS, but the cortisol response was not different on a log scale. To further investigate the pituitary-adrenal differences between the two breeds, the 24-hr profile of ACTH and cortisol plasma concentrations, a corticotropin-releasing factor (CRF) and a coupled dexamethasone-ACTH test were studied. Five castrated male 9-wk-old piglets from each breed were fitted surgically with a jugular vein catheter. A classic marked circadian rhythm of cortisol and a weak nycthemeral variation of ACTH were found. Cortisol concentrations were approximately twice higher in MS exclusively during the early light phase (from 0800-1200 hr) of the cycle, but no significant interbreed difference was found in the circadian rhythm of ACTH. Administration of CRF (1 microgram/kg iv) induced the same significant increase in plasma ACTH and cortisol concentrations in both breeds. Administration of ACTH (10 micrograms/kg i.v.) increased significantly cortisol concentrations and revealed no difference in plasma cortisol response to ACTH. These data suggest that the hypercortisolism of MS pigs is of adrenal origin, and related to extrapituitary factors that control the adrenal sensitivity during the light phase of the diurnal cycle.

Adaptation, Physiological↗

PubMed1999

Serotonin and stress.

Forty-five years after its discovery, brain serotonin (5-HT) is still the subject of intense research aimed at understanding its role in stress adaptation. At the presynaptic level, numerous stressors increase nerve firing and extracellular 5-HT at the level of serotonergic cell bodies or nerve terminals. Different studies have reported stressor- and region-specific changes in extracellular 5-HT, a view challenged by electrophysiological and neurochemical evidence for a nonspecific response of serotonergic neurones to stressors when activity/arousal is taken into account. In addition, early studies indicate that stress-induced elevation in 5-HT synthesis, a key counter-regulatory process allowing serotonergic homeostasis, is mediated by specific neuroendocrine mechanisms. In addition to the multiplicity of postsynaptic 5-HT receptors and their specific regulation by corticoids, specificity to stressors is also underscored when considering one receptor type such as the 5-HT1A receptor. Stress studies should consider the past experience and the genetic status of the individual as key modulators of the serotonergic responses to stress.

Animals↗

PubMed1999

Identification of female-specific QTLs affecting an emotionality-related behavior in rats.

The influence of genetic factors on psychological traits and disorders has been repeatedly demonstrated; however, the molecular mechanisms underlying such an influence remain largely unknown. Anxiety-related disorders constitute the most common class of mental disorder in humans, with women being diagnosed far more frequently than men. A better understanding of the genetic and gender-related mechanisms mediating anxiety traits should enable the development of more rational methods for preventing and treating anxiety disorders. In this study we have aimed to identify, for the first time, quantitative trait loci (QTL) influencing anxiety/emotionality-related traits in rats. To this end, two strains-Lewis (LEW) and Spontaneously Hypertensive Rats (SHR)-that differ for several behavioral measures of anxiety/emotionality were intercrossed. A QTL analysis of the F2 population revealed suggestive loci for various traits, including behaviors in the elevated plus-maze and blood pressure. In addition, one major QTL explaining 50.4% of the total variance (LOD = 7.22) was identified on chromosome 4 for the locomotion in the central and aversive area of the open field. Two other relevant QTLs have been recently mapped near this chromosomic region in the rat, which also harbors Tac1r, the gene encoding for the substance P receptor. Our major QTL affected females but not males and its effect depended on the type of cross (LEW or SHR grandmothers). The present results reveal a complex genetic basis underlying emotional behaviors and they confirm the existence of interactions between genetic factors and sex for this kind of trait. Further investigation of the loci identified herein may give clues to the pathophysiology of psychiatric disorders such as anxiety-related ones.

Animals↗