Peripubertal stress of male,but not female rats increases morphine-induced conditioned place preference and locomotion in adulthood

Animal studies demonstrate that peripubertal social stress markedly increases the risk for subsequent substance use in adulthood. However, whether non-social stress has a similar long-term impact is not clear, and whether male and female animals show different sensitivity to peripubertal non-social stress has not been examined. In the present study, we addressed these issues by introducing two non-social stressors (elevated platform and predator odor 2,5-Dihydro-2,4,5-trimethylthiazoline) to male and female Wistar rats during adolescence (postnatal days 28–30, 34, 36, 40, and 42), then tested reward-related behaviors during adulthood, including morphine-induced conditioned place preference (CPP, 1 mg/kg morphine or 5 mg/kg morphine) and hyperlocomotor activity (5 mg/kg morphine). We found that adult male rats, but not females who were exposed to peripubertal non-social stressors showed enhanced morphine-induced CPP. Moreover, morphine-induced increase in locomotor activity was also significantly increased in adult male rats, but not in females. These results indicate that peripubertal exposure to repeated non-social stress may enhance sensitivity to the rewarding effects of opioids in adulthood in a sex-dependent manner, with males being even more sensitive than females in this regard.     

Strain differences in sleep patterns of healthy and influenza-infected inbred mice

Influenza-infected C57BL/6J and BALB/cByJ mice respectively develop increased slow-wave sleep (SWS) during the dark phase and reduced SWS during the light phase of the 24 hour circadian cycle. To determine whether similar or alternative variations in SWS develop after influenza infection in other inbred strains of mice, we characterized the sleep patterns of additional strains both before and after influenza infection. Three strains (A/J, BALB/cByJ, and C3H/HeJ) showed light-phase SWS suppression, two strains (C57BL/6J and DBA/2J) showed dark-phase SWS enhancement, and one strain (A/J) showed dark-phase SWS suppression. Three strains (AKR/J, C57BR/cdJ, and FVB/NJ) did not show significant changes in SWS time on day two post-inoculation. Core temperatures were correlated to change in SWS time after infection, but were not correlated to SWS during the baseline period. These data support and expand the existing literature that indicates genetic modulation of sleep both in healthy mice and in mice undergoing viral infection.     

Salt preference in desalivate rats

Desalivate rats were tested in two-bottle preference tests for a 0.4% NaCl solution under different dietary conditions. Two effects were seen. A loss in preference may occur because of the prandial drinking pattern desalivates show. Elimination of prandial drinking abolished this effect. An enhancement in preference is seen with a diet that presumably initiates a prandial drinking pattern insufficient for taste masking, or when food is absent. Apparently desalivation has a direct enhancing effect on salt preference that may be exaggerated under appropriate dietary conditions.     

Environmental factors in hand preference formation: Evidence from attempts to switch the preferred hand

We surveyed 650 young adults to assess both their current handedness behaviors and past attempts to shift their hand preference. We found that 73 (11.2%) individuals had experienced hand preference change attempts and 52 (8.0%) had undergone pressure to switch hand preference to the right. The likelihood that an individual had experienced pressure to change hand use was not related significantly to gender or to a number of familial factors. However, the success of the hand change varied with gender; females reported greater success in shifting their handedness.This research was supported by grants from the Natural Sciences and Engineering Research Council of Canada, the University of Victoria Committee on Faculty Research and Travel, and St. Lawrence University. We thank T. Gallagher, B. Kovar, K. Salter, W. Wong, and K. Wright for their assistance in data collection and T. Allen for his assistance in data analysis.     

褪黑素抑制可卡因诱导的条件性位置偏爱大鼠DNMT1的下调

目的研究褪黑素拮抗大鼠可卡因诱导的条件性位置偏爱的作用和可能机制。方法建立可卡因诱导的条件性位置偏爱模型,诱导前30min给予褪黑素腹腔注射,检测实验大鼠条件性位置偏爱的变化,并应用Western blot、免疫荧光共聚焦激光扫描显微镜及real-time PCR技术,检测褪黑素对大鼠前额叶皮层中可卡因诱导的DMNT1表达的影响。结果褪黑素对可卡因诱导的大鼠条件性位置偏爱效应具有显著的抑制作用。共聚焦显微镜和Western blot结果表明,可卡因诱导大鼠前额叶皮层中DNMT1表达的减少,而褪黑素能够抑制可卡因的这种作用。Real-time PCR检测结果证明,可卡因诱导大鼠前额叶皮层中DNMT1 mRNA的下调,而褪黑素能够抑制这种作用。结论褪黑素可能通过抑制大鼠前额叶皮层中DNMT1表达的下调拮抗可卡因诱导的条件性位置偏爱。     

Strain and colony differences in the neurotoxic sequelae of MK-801 visualized with the amino-cupric-silver method

The strain and sex of a species under investigation may influence the animal's physiological response to a variety of stimuli. Strain and sex differences are important considerations when evaluating animal models. In the rodent MK-801 model of schizophrenia, degenerative changes occur widely in the main olfactory system and in a number of cortical brain regions. In the present report, we compare the effects of MK-801 neurotoxicity in two strains of female rats and also two lines within each strain. The magnitude and regional extent of the neurodegeneration detected with the amino-cupric-silver method varied markedly both between the Sprague-Dawley and Wistar rat strains and also between two lines derived from each strain. For example, terminal degeneration occurred in layer VI of somatosensory cortex and the central extended amygdala in Sprague-Dawley but not Wistar rats. Moreover, MK-801 treatment led to somatodendritic degeneration in the dentate gyrus of the dorsal hippocampus and basolateral amygdala in Wistar rats from Charles River Laboratories but not those from Ferreyra Institute. There are thus both strain and intrastrain differences in the magnitude of the neurodegenerative response to MK-801 treatment. The differing neurotoxicity of MK-801 between rat strains and between lines within a strain may reflect genetic variation and/or differences in hepatic biotransformation and thus the bioavailability of the drug between strains and lines within a strain.     

Strain differences in rats with respect to speed of conflict resolution

Speed of conflict resolution was studied in a conditioned punishment paradigm in a Skinner box and a straight runway. In both experimental situations speed of conflict resolution was defined as the latency to gain food during an approach-avoidance conflict. In the Skinner box Tryon Maze Bright rats were faster in speed of conflict resolution than Tryon Maze Dull rats, and Roman Low Avoidance rats were faster than Roman High Avoidance rats. In the runway situation, Wistar Kyoto rats were faster in solving the conflict than randomly bred Wistar Wu rats and Brown Norway rats were faster than Wistar Wu rats. Differences between the strains in speed of conflict resolution could not be consistently explained from strain differences in approach or avoidance behavior, measured separately. It is, therefore, suggested that speed of conflict resolution is a unique parameter.This investigation was supported by grants from the Netherlands Psychonomics Foundation (NWO No. 15-26-12 and NWO No. 15-25-28).     

Nicotine-induced conditioned place preference in adolescent and adult rats

About 1 million American adolescents start smoking every year. Adolescents may be unusually sensitive to certain consequences of nicotine, demonstrating, for instance, significantly higher rates of dependence than adults at the same level of nicotine use. To explore whether adolescents may be more sensitive to rewarding properties of nicotine than adults, the present study used an animal model to assess the rewarding effects of a low nicotine dose (0.6 mg/kg) in a conditioned place preference (CPP) paradigm. Locomotor activity during conditioning and testing was also evaluated. Nicotine was observed to induce place preference conditioning in adolescent Sprague-Dawley rats, whereas the training dose of 0.6 mg/kg failed to produce convincing place preference in their adult counterparts. Age differences were also apparent in terms of nicotine influences on motor activity, with adults being more sensitive to nicotine-suppressant effects and only adolescents showing an emergence of nicotine-stimulatory effects upon repeated exposures. An increased predisposition to stimulatory nicotine effects during adolescence may contribute to age-specific rewarding properties of the drug as revealed using the CPP paradigm in this experiment. Increased sensitivity to stimulatory and rewarding effects during adolescence could potentially contribute to the high rate of nicotine use and dependence among human adolescents.     

Sexual and olfactory preference in noncopulating male rats

In some species including rats, mice, gerbils, and rams, apparently normal males fail to copulate when repeatedly tested with receptive females. These animals are called "noncopulators (NC)," and the cause of this behavioral deficit is unknown. It has been shown that NC rats do not have hormonal alterations or deficits in the mechanisms that control penile function. The present study was designed to examine (Experiment 1) whether NC male rats prefer receptive females to sexually active males. In addition, the olfactory preference for bedding soiled from estrous or for anestrous bedding was investigated. These tests were performed in NC and copulating (C) male rats when the subjects were intact, gonadectomized (GDX), or GDX and treated with high doses of testosterone propionate (TP). Our results demonstrate that NC rats do not display sexual behavior even after high TP treatment. While C male rats have a clear preference for receptive females as opposed to a sexually active male, NC rats do not. In all hormonal conditions, the preference shown by NC rats for estrous bedding was significantly reduced in comparison to that seen in C rats. TP treatment in NC rats did not modify either partner or odor preference. In Experiment 2, we evaluated if NC rats are feminized and if it could be easier to induce feminine-like behavior by hormone treatment with estradiol benzoate (EB) or with EB plus progesterone (P) (EB+P). Odor preference for estrous or male bedding under these hormonal conditions was also compared. No differences between NC and C rats were found in feminine sexual behavior. In the olfactory test, we found that NC rats prefer odors from receptive females as opposed to male odors, but this preference is reduced compared to that of C rats. Males treated with EB or EB+P show no preference for female odors. These results demonstrate that treatment with EB or EB+P does not increase feminine sexual behavior in NC rats.     

Circadian and sex differences in hyperactivity produced by amphetamine in rats

Hyperactivity produced in rats with d-amphetamine HCl was measured using a residential maze. Groups of 4 male or 4 female rats were kept on a 12-hr light, 12-hr dark schedule. Amphetamine was given 4 hr after onset of either the light or dark cycle and activity measured for the following 8 hr. For all doses of amphetamine (in light or dark), females displayed significantly greater increases over control activity than males. The results suggested that the greater activity of female rats was not due solely to the recognized sex difference in amphetamine metabolism, but rather there was a sex-related difference in the CNS. Previous experiments have shown that neonatal asphyxia and x-irradiation in utero produce greater hyperactivity in female than in male rats. It is proposed that female rats are more likely to develop hyperactive behavior.     

Strain differences in the sleep of rats

Sleep was measured in two inbred rat strains (Lewis and Brown Norway) and their F1 hybrids to investigate patterns of inheritance and to provide a starting point for future studies of F2 and recombinant rats. Recordings from chronically implanted electrodes were quantified and scored by a computerized system; results were evaluated by an analysis of variance with pairwise comparisons by the Tukey HSD test. Brown Norway rats had the highest paradoxical sleep (PS) percentages; Lewis rats had the lowest. Hybrid rats had PS percentages intermediate between parent strains and significantly different from both. These results suggest codominance or multigenic transmission of PS amounts. There were no group differences of number of PS bouts; Brown Norway and hybrid rats had longer bouts than Lewis rats. Lewis and hybrid rats had similar amplitudes of the diurnal rhythm of PS, which were higher than those of Brown Norway rats; single gene transmission remains possible for diurnal rhythm amplitude. Thus, inheritance of PS percentage and rhythm amplitude appear independent. No group differences in PS latency were found.     

Transplantation of the neonatal suprachiasmatic nuclei into rats with complete bilateral suprachiasmatic lesions

The suprachiasmatic nuclei (SCN) obtained from neonatal day 1 rats were transplanted into the third ventricle of SCN lesioned rats which had shown circadian arrhythmicity in wheel-running activity for more than 2 months. In 8 out of 16 rats that received SCN transplantation, appearance of circadian rhythms in wheel-running activity was observed between 2 and 9 weeks after transplantation. Histological examination revealed ingrowth of the grafts into the periventricular zone, caudal from the lesioned SCN. These findings suggest that the recovery of circadian rhythmicity was the result of functional reinnervation of the periventricular zone by efferent fibers from the SCN.     

Effects of two-hour light-dark cycles on feeding, drinking and motor activity of the rat

The effect of two-hour light-dark cycles on feeding, drinking and motor activity in the rat was compared with behavior under the usual $\text{12}\text{12}$ hour cycle. The two-hour cycles consisted of $\text{60}\text{60}$ min, $\text{80}\text{40}$ min and $\text{40}\text{80}$ min light-dark schedules which were maintained each for 7 days. Water intake, frequency of feeding, and motor activity were still significantly higher during dark than during light, although their occurrence during dark was reduced as compared to the $\text{12}\text{12}$ hour control schedule. A free-running circadian rhythm of consummatory behavior with a period length exceeding 24 hours was present throughout the experimental period. The amplitude of the circadian feeding rhythm gradually decreased over time, whereas the percentage of feeding during dark increased. During the circadian phase of minimal food intake, illumination changes affected feeding behavior more strongly than during the phase of maximal food intake. After restoration of the orginal $\text{12}\text{12}$ hour cycle, the amplitude of the nocturnal feeding rhythm increased gradually over several days, whereas the amplitude of the drinking rhythm showed a more rapid recovery. The experiments show that even short cycles of illumination may exert control over the rat's consummatory and motor activity. Short light-dark schedules provide a way for studying separately effects of illumination and of circadian rhythms.     

大鼠大脑白质及白质内有髓神经纤维的性别与年龄差异

目的:研究正常年轻和中老年组雌雄性大鼠大脑白质及白质内有髓神经纤维之间的性别差异,并探讨大脑发育过程中性别差异随年龄增加的改变。方法:运用透射电子显微镜和体视学方法对6~8月龄的年轻Long-Evans大鼠及18月龄同种中老年大鼠大脑白质及其有髓神经纤维进行定量研究。结果:年轻组雄性大鼠大脑白质、有髓神经纤维及其髓鞘的总体积均显著大于雌性,而中老年组雌性大鼠大脑白质、有髓神经纤维体积密度、有髓神经纤维及其髓鞘的总体积均显著大于雄性。结论:年轻组及中老年组大鼠大脑白质、白质内有髓神经纤维及其髓鞘总体积均存在性别差异,随着年龄的增长,雄性大鼠大脑白质及白质内有髓神经纤维体积的减少较雌性更为明显。     

Effects of cocaine place conditioning, chronic escalating-dose "binge" pattern cocaine administration and acute withdrawal on orexin/hypocretin and preprodynorphin gene expressions in lateral hypothalamus of Fischer and Sprague-Dawley rats

Recent evidence suggests an important role for hypothalamic orexins/hypocretins in modulation of drug reward and addiction-like behaviors in rodents. Our recent study has shown that the aversive state of arousal during acute morphine withdrawal is associated with increased orexin gene expression in lateral hypothalamus (LH) of Fischer 344 (F344) inbred rats, with no change in the expression of preprodynorphin (ppDyn), a gene co-expressed with LH orexin. Therefore, we determined whether orexin and ppDyn mRNA levels in LH or medial hypothalamus (including perifornical and dorsomedial areas) of F344 or Sprague-Dawley (SD) outbred rats, are altered following: 1) cocaine (10 mg/kg, i.p.) conditioned place preference (CPP); 2) chronic (14 days) cocaine exposure using both "binge" pattern administration in steady-dose (45 mg/kg/day) and escalating-dose (45-90 mg/kg/day) regimens; and 3) acute (1 day) and chronic (14 days) withdrawal from cocaine with opioid receptor antagonist naloxone treatment (1 mg/kg). We found that orexin mRNA levels were decreased after cocaine place conditioning in the LH of SD rats. A decreased LH orexin mRNA level was also observed after chronic escalating-dose cocaine (but not CPP pattern regimen without conditioning, or steady-dose regimen) in both strains. In F344 rats only, acute withdrawal from chronic escalating-dose cocaine administration resulted in increases in both LH orexin and ppDyn mRNA levels, which were unaltered by naloxone or after chronic withdrawal. Our results suggest that (1) alteration of LH orexin gene expression is region-specific after cocaine place conditioning in SD rats and dose-dependent after chronic exposure in both strains; and (2) increased LH orexin and ppDyn gene expressions in F344 rats may contribute to negative affective states in cocaine withdrawal.     

Effect of gonadectomy on taste preference for glucose solutions in rats.

Mature male and female rats maintained on an ad lib diet were given a choice between tap water and glucose solutions of different concentrations (1, 5 and 12 percent). Both sexes exhibited a definite preference for the 12 percent glucose solution, but the females drank significantly more than males. Gonadectomy produced neither quantitative nor qualitative changes in the choice made by male rats. On the contrary, gonadectomized females showed a depression of the 12 percent glucose solution intake and an increase in the 5 percent glucose solution intake, resulting in a decrease of the total fluid intake. A comparison of ovariectomized and intact female rats in regard to the self-selection of tap water and a 5 percent glucose solution confirmed the stimulatory effect of ovariectomy on the 5 percent glucose solution intake. When a choice between tap water and 12 percent glucose solution was permitted the ovariectomized rats showed a weaker positive response to the sweet solution than the intact female rats.     

Low-dose pretreatment with clorgyline decreases the levels of 3-methoxy-4-hydroxyphenylglycol in the striatum and nucleus accumbens and attenuates methamphetamine-induced conditioned place preference in rats

The effect of treating rats with clorgyline, an irreversible monoamine oxidase-A (MAO-A) inhibitor, on methamphetamine (METH)-induced conditioned place preference (CPP) was investigated. Administering rats with METH (1.0 mg/kg i.p.) every other day during two conditioning sessions (i.e., saline/METH conditioning with no clorgyline pretreatment) induced a significant CPP compared with saline/saline conditioning. Pretreatment of the rats with clorgyline at a dose of 0.1 mg/kg (i.p.), but not 1.0 or 10 mg/kg, attenuated the METH-induced CPP. Neurochemical analysis using high-performance liquid chromatography revealed that the tissue levels of monoamines and their metabolites were not significantly affected by treatment with 0.1 mg/kg clorgyline except for the levels of 3-methoxy4-hydroxyphenylglycol (MHPG) in the striatum and nucleus accumbens (NAc). Clorgyline at doses of 1.0 or 10 mg/kg significantly affected the tissue levels of 3,4-dihydroxyphenylacetic acid, norepinephrine (NE), MHPG, and serotonin in the cerebral cortex and those of all monoamines and metabolites examined in the striatum and NAc. A significant decrease in the MHPG/NE ratio in the striatum and NAc was apparent in the rats pretreated with 0.1 mg/kg clorgyline. Overall, the present study demonstrated that low-dose clorgyline attenuated METH-induced CPP in rats.     

Social dominance and stress-induced hypertension: Strain differences in inbred mice

Agonistic encounters in socially unstable dominance hierarchies have been assumed to produce stress-induced hypertension in mice. Studies of this phenomenon have used the CBA mouse strain. Given the possible strain specificity of the social behavior-hypertension relationship, the present study investigated DBA/2j and C57BL/6j strains. Systolic blood pressures were obtained before and after preisolated males were either group housed or isolated. The body and adrenal weights, tail wounds and territory patrol measurements were also taken. The DBA/2j strain replicated the previous findings for CBA mice. However, the C57BL/6j strain did not show evidence of social dominance or hypertension. The C57BL/6j mice were apparently genetically predisposed to respond differently to the experimental conditions. Hypertension was correlated with dominance interaction rather than social instability.     

A simplified triple-test cross analysis of alcohol preference in the rat

Reanalyses of first-degree biometrical genetic data from previous studies of alcohol preference in the mouse revealed little consistency beyond a basic additive genetic component. A simplified triple-test cross in the rat investigated the genetic architecture of alcohol preference for a 10% (w/v) alcohol solution or water. An initial survey of eight selected and inbred strains identified high- and low-scoring strains, the MNR and the ACI, respectively, which were crossed as tester lines to six strains (the RHA, RLA, TMB, TMD, MNR, and ACI) to produce the required set of largely F₁ families. The additive-dominance model proved adequate for males, and directional dominance for low alcohol preference was found on all three measures: alcohol intake, alcohol preference ratio, and alcohol calorie contribution ratio. For females the model was adequate only for alcohol preference ratio, which showed ambidirectional dominance. The relevance of such genetic architecture to an animal model of alcoholism and to the evolution of alcohol drinking in the rat is discussed.This work was supported by a grant from the Medical Research Council of Great Britain to Professor J. L. Jinks and the second author and by a postgraduate studentship from the council to the first author.     

Synthetic progestins and sweetness preference in intact female Sprague-Dawley rats

Intact Sprague-Dawley female rats were treated with 0.25 μg or 1.25 μg ethinyl-estradiol (EE) in combination with one of 3 synthetic progestins: (5 μg) norethindrone, norethynodrel, or norgestrel. In Experiment 1 both dosages of EE in combination with the synthetic progestins suppressed sweetness preference, with a somewhat greater effect for the 1.25 μg EE dosage. Norgestrel in combination with EE produced the longest suppression of sweetness preference. In Experiment 2 progestins administered in the absence of EE showed no significant effect on sweetness preference. When 1.25 μg EE was administered singularly, a significant decline in sweetness preference occurred, but not as great a decline as in combination with a progestin.