The effects of early handling on latent inhibition in male and female rats

Latent inhibition (LI) is a behavioral paradigm in which repeated exposure to stimuli not followed by meaningful consequences renders these stimuli ineffective for subsequent learning. The development of LI is considered to reflect learning not to attend to, ignore, or tune out irrelevant stimuli. The present study investigated the differences in the development of LI between handled and nonhandled males and females. Infantile handled (Days 1-22) and nonhandled, male and female Wistar rats were tested in maturity in the LI paradigm. The LI procedure consisted of two stages: pre-exposure, where animals received 60 presentations of the to-be-conditioned stimulus (tone) and test, where the animals acquired a two-way active avoidance response with the tone serving as the warning signal. Handled animals reached higher percentage of avoidance responses as compared with nonhandled animals. Latent inhibition was obtained in both the handled and the nonhandled females, but only the handled males showed the LI effect. Nonhandled males failed to develop LI. The results indicate that the effects of handling are evident in learning tasks that do not involve motivational-emotional variables, i.e., learning to ignore irrelevant stimuli; handling differentially affects males and females, with a much greater impact on males and the nonhandling procedure has significant deleterious consequences on adult behavior.     

Differential effects of choline administration on liver microsomes of female and male rats

Choline was administered for 3 weeks, twice daily, in the amount of $\text{50}\text{mg}\text{100}\text{g}$ body weight to male and female rats. The content of phosphatidyl cholines (PC) and the enzymatic activities related to the smooth endoplasmic reticulum were increased in the female rats receiving choline but not in males. Such changes were accompanied by an increase in surface of smooth membranes, evaluated by stereological analyses. Both enzymatic activities and values of surface and volume densities of the endoplasmic reticulum were lower in the untreated females than in the corresponding group of males. Morphological electron microscopic findings well agree with the increased biogenesis of smooth surfaced membranes in the hepatocytes of the liver of female rats receiving choline.     

Effects of prepubertal handling on shock-induced fighting and ACTH in male and female rats.

Rats which received either handling from Days 1–14 (EH) or 22–35 (LH) of life or no handling (NH) were tested in the shock-induced fighting situation in adulthood. Ten males and 10 females from each group were either paired for fighting (F), shocked singly (S), or received no shock (N) in the test chamber for 4.5 min in 3 sessions given 48 hr apart. Immediately after the third test session, trunk blood was obtained for determination of plasma ACTH concentrations. Males and females did not differ with respect to fighting frequency in response to shock, but males displayed the fighting posture substantially more than did females. Rats handled either preweaning (EH) or postweaning (LH) fought more often at the two lower shock intensities (0.5 and 1.3 mA) than did nonhandled controls (NH). The incidence of fighting positions did not differ as a function of prior handling. In all groups but one, the pattern of ACTH response to the different test conditions coincided with previous reports: higher levels of ACTH were found in response to shock alone than in response to fighting plus shock, and the lowest levels were found in the nonshocked controls. In the exceptional group, the NH males (but not females), there was a nondiscriminatory ACTH response to the S and F test conditions. The effects of prior handling are discussed in terms of an enhanced coping ability. The results point to the importance of comparing both pre- and postweaning groups when studying the handling phenomenon.     

Ghrelin effects on gonadotropin secretion in male and female rats

Ghrelin is a 28-amino acid peptide primarily involved in the control of food intake and growth hormone secretion. The present experiments were carried out to analyze the potential involvement of ghrelin in the control of gonadotropin secretion. Prepubertal intact and gonadectomized female and male rats, cyclic rats in diestrus, lactating rats and aged female rats were i.c.v. injected with ghrelin (3 nmol/rat) and blood samples were obtained by decapitation 15 min later. In addition, we analyzed the effects of ghrelin on in vitro basal and luteinizing hormone-releasing hormone (LHRH)-stimulated gonadotropin secretion. Our present results indicate that ghrelin inhibited luteinizing hormone (LH) secretion in vivo in prepubertal males as well as gonadectomized males and females, whereas follicle-stimulating hormone (FSH) remained unaffected. In vitro, ghrelin stimulated the secretion of both gonadotropins, and differentially modulated the response to LHRH; the LH response was inhibited, while the FSH response was enhanced. Overall, our current data open up the possibility that ghrelin may be involved in the control of LH secretion, and in the dissociation of both gonadotropins that takes place in many physiological, pathological and experimental situations.     

Differential effects of cuts through the posterior hypothalamus on food intake and body weight in male and female rats

Large knife cuts in the coronal plane through the posterior hypothalamus which transected the caudal connections of the medial hypothalamus without producing significant direct damage to cellular components of the region resulted in a very marked increase in food intake and rate of weight gain in female rats, but had little or no effect in male rats of the same strain. Water intake was equally elevated in both sexes. A detailed analysis of the effects of smaller cuts in the same region indicated that the pathways that are responsible for the effectiveness of the larger cuts do not course through the region immediately behind the ventromedial nuclei (VMN) but, instead, through the perifornical region lateral and posterior to the VMN. In the female, hyperphagia is not seen after cuts behind the VMH or lateral to the fornix but all cuts that invade the perifornical region to a significant extent result in overeating and obesity. In the male, a very mild hyperphagia (but no obesity) is seen after cuts that are restricted to this perifornical region but larger cuts that involve even minor aspects of the lateral hypothaalmus (LH) are entirely ineffective. Analysis of the effects of cuts that involve the medial, perifornical, and lateral hypothalamus to varying extent suggested that the disinhibitory effects of perifornical transections may be counteracted by relatively strong inhibitory effects due to damage to fibers in the lateral hypothalamus in the male, where the influence of the perifornical system appears to be weak, but not in the female, where the influence of the perifornical system appears to be very strong. The marked sex differences which characterize the effects of all cuts on body weight indicate that the perifornical system may be concerned specifically with metabolic functions that contribute to the development and/or maintenance of the organism's setpoint for body weight.     

Effects of neonatal handling on the basal forebrain cholinergic system of adult male and female rats

Neonatal handling is an early experience which results in improved function of the hypothalamic-pituitary-adrenal axis, increased adaptability and coping as a response to stress, as well as better cognitive abilities. In the present study, we investigated the effect of neonatal handling on the basal forebrain cholinergic system, since this system is known to play an important role in cognitive processes. We report that neonatal handling results in increased number of choline-acetyl transferase immunopositive cells in the septum/diagonal band, in both sexes, while no such effect was observed in the other cholinergic nuclei, such as the magnocellular preoptic nucleus and the nucleus basalis of Meynert. In addition, neonatal handling resulted in increased M1 and M2 muscarinic receptor binding sites in the cingulate and piriform cortex of both male and female rats. A handling-induced increase in M1 muscarinic receptor binding sites was also observed in the CA3 and CA4 (fields 3 and 4 of Ammon's horn) areas of the hippocampus. Furthermore, a handling-induced increase in acetylcholinesterase staining was found only in the hippocampus of females. Our results thus show that neonatal handling acts in a sexually dimorphic manner on one of the cholinergic parameters, and has a beneficial effect on BFCS function, which could be related to the more efficient and adaptive stress response and the superior cognitive abilities of handled animals.     

Differential effects of testosterone on protein synthesis activity in male and female quail brain

In Japanese quail, testosterone (T) increases the Nissl staining density in the medial preoptic nucleus (POM) in relation to the differential activation by T of copulatory behavior. The effect of T on protein synthesis was quantified here in 97 discrete brain regions by the in vivo autoradiographic (14)C-leucine (Leu) incorporation method in adult gonadectomized male and female quail that had been treated for 4 weeks with T or left without hormone. T activated male sexual behaviors in males but not females. Overall Leu incorporation was increased by T in five brain regions, many of which contain sex steroid receptors such as the POM, archistriatum and lateral hypothalamus. T decreased Leu incorporation in the medial septum. Leu incorporation was higher in males than females in two nuclei but higher in females in three nuclei including the hypothalamic ventromedial nucleus. Significant interactions between effects of T and sex were seen in 13 nuclei: in most nuclei (n=12), T increased Leu incorporation in males but decreased it in females. The POM boundaries were defined by a denser Leu incorporation than the surrounding area and incorporation was increased by T more in males (25%) than in females (6%). These results confirm that protein synthesis in brain areas relevant to the control of sexual behavior can be affected by the sex of the subjects or their endocrine condition and that T can have differential effects in the two sexes. These anabolic changes should reflect the sexually differentiated neurochemical mechanisms mediating behavioral activation.     

Acute effects of aspartic acid on ventilation of male and female rats

The effects of aspartic acid (aa) on ventilation were evaluated in awake male and female rats prior to and 15, 30, and 45 minutes after saline, 100 mg/kg or 580 mg/kg aa was injected subcutaneously. Subsequently, rats were exposed to hypoxic and hypercapnic gas challenges. In males, 100 mg/kg aa increased ventilation (VE) by increasing inspiratory flow rate (VT/TI), tidal volume (VT), and frequency of breathing (f) by 30 minutes, whereas in females VT was increased above saline levels only at 15 minutes. VE did not decrease over time. A dose of 580 mg/kg aa depressed ventilation in males for 2 hours by decreasing VT, VT/TI and f. In contrast, female rats exhibited a decreased ventilation only at 15 minutes which then began to return to saline levels by 45 minutes. Neither male nor female rats treated with either dose of aa showed a depressed response to hypoxia or hypercapnia. These data indicate that aa at two doses can affect the pattern of ventilation differently in male and female rats. One mechanism responsible for the differences noted between the two groups is the effect aspartic acid may have on testosterone production. An additional study comparing ventilatory responses of sham operated and castrated males to various doses of aa indicated that testosterone was not necessary to show the 'male' pattern of response.     

Differential effects of yohimbine and naloxone on copulatory behaviors of male rats

Prior research has demonstrated that both yohimbine, an alpha2-adrenergic antagonist, and naloxone, an opiate antagonist, facilitate components of copulatory behaviors in nonstressed male rats. In the present experiments, we demonstrate that these drugs differentially affect copulatory behaviors when the behavioral testing situation contained an aversive element. Male rats received an injection of lithium chloride (0.3 M, 20 ml/kg, ip) immediately after each encounter with an estrous female. Consequently, male copulatory behaviors gradually declined during successive test sessions. These male rats also received ip injections of either yohimbine (2 mg/kg/ml), naloxone (4 mg/kg/ml), or isotonic saline 20 min prior to each copulation test. Yohimbine-treated rats were more likely to copulate than control rats during both acquisition and extinction of lithium chloride-induced associative inhibition of copulatory behavior. Conversely, naloxone-treated rats were less likely to copulate than control rats during both acquisition and extinction. These data are consistent with the hypothesis that yohimbine increases sexual motivation in the male rat and limit the generality of the excitatory effects of naloxone on copulatory behaviors.     

Transgenerational effects of infantile adversity and enrichment in male and female rats

To discover whether the accumulation of life's experiences, adverse and enriching, inform, and serve the following generation by inheritance we examine whether stress to a weanling female will influence her future offspring, whether prereproductive enrichment to the dam, or postweaning enrichment to the offspring, can reverse the transgenerational effects of stress, and whether, like adversity, enrichment might have transgenerational effects. Female rats were exposed to stressors when they were 27-29 days old. Half of these females and their controls were then raised in an enriched environment from weaning until mating at 60 days to examine whether preproduction enrichment reverses the effects of preproduction stress on offspring. Half of the offspring of each group were raised in an enriched environment after weaning, to see whether it reverses the effects of preproduction stress and buttresses prereproductive enrichment. Behavior was examined in 625 adult offspring in 16 groups covering all permutations of the experimental variables (preproduction weanling stress (PS), preproduction enrichment (PE), offspring enrichment (OE), sex). Exploration, avoidance learning, startle, and social interaction were tested. Results reveal that very early prereproductive experience in females, adverse or enriching, will transgenerationally influence their future offspring, depending on the behavior tested and sex. Our finding that enrichment, whether to the parent or offspring generation, can ameliorate the transgenerational impact of adversity, has novel implications for the malleability of transgenerational inheritance, and its individual, social, and therapeutic impact.     

Organizational and activational effects of gonadal steroid hormones on the EEG of male and female rats

To analyze organizational and activational effects of sex steroids on adult rat electroencephalographic activity (recorded at postnatal day 100), seven groups were included: males (48)-intact, neonatally or adult castrated; females (64)-intact, ovariectomized and exposed pre- or neonatally to testosterone propionate. In males, neonatal orchidectomy increased beta relative power, whereas both neonatal and adult castration reduced interparietal correlation. In females, prenatal testosterone administration produced higher theta absolute power; theta relative power was higher in all experimental groups, whereas beta1 and beta2 were decreased by prenatal and increased by neonatal virilization; prenatal virilization enhanced, while neonatal virilization and adult ovariectomy decreased interparietal correlation. These data indicate that females are more sensitive to early prenatal than to neonatal organizational effects of sex steroids, and some electroencephalographic features are feminized in castrated males and virilized in perinatally androgenized females.     

Kindling-induced emotional behavior in male and female rats

Modeling fear in animals is a critical approach for identifying the neural mechanisms involved in human disorders such as generalized anxiety and panic. Amygdala kindling has proven useful in this regard because it produces dramatic increases in fearful behavior. The purpose of this experiment was to compare the behavioral effects of kindling in male and female rats. Compared with the sham-stimulated rats, the kindled male and female rats showed similar increases in fearful behavior, with some sex differences in fear-related open-field activity. They also showed decreased immobility in the forced-swim test and increased sucrose consumption. These results suggest that kindling-induced fear is generally similar in male and female rats and that kindling does not appear to induce depression-like behavior.     

Allylglycine-induced seizures in male and female rats.

The possibility that a sex difference in gamma-aminobutyric acid (GABA) activity might be an underlying cause of the previously reported sex differences in picrotoxin-induced seizures was investigated. Male and female rats were injected (IP) with the GABA antagonist, L-allylglycine (100, 150, 200, or 250 mg/kg), and observed for behavioral signs of five categories of seizures induced by picrotoxin: myoclonic, focal, generalized tonic extension, generalized clonic, and generalized seizures with tonic and clonic components. The latency to the first occurrence of each seizure category was scored. Of the five categories of seizures investigated, only focal and generalized tonic extension seizures were observed after allylglycine in the doses tested. Female rats were significantly more susceptible than male rats to allylglycine-induced focal (p less than 0.007) and generalized tonic extension (p less than 0.05) seizures. The results suggest that male-female differences in presynaptic GABA activity may have relevance for sex differences in the occurrence of focal and tonic extension seizures. Differences in the seizure profiles associated with allylglycine and picrotoxin suggests that pre- and postsynaptic antagonism of GABA activity may have different consequences for specific seizure categories and the sex differences associated with those categories.     

Effect of sibutramine on macronutrient selection in male and female rats

Sibutramine, a serotonin-noradrenaline reuptake inhibitor (SNRI), has been shown to be a safe and effective weight-loss drug. The purpose of the present study was to examine whether sibutramine has an effect on macronutrient selection in both female and male rats in addition to total food intake. Wistar rats of both sexes were divided into three groups, and each group was offered a different set of three sensorily contrasting macronutrient-specific diets, each set including carbohydrate-, protein-, and fat-rich diets. Sibutramine (10 mg/kg) was shown to consistently decrease carbohydrate and fat intake at all data points regardless of gender and diet. Intake of carbohydrate differed between male and female rats at 2 h post administration with 2.5 and 5 mg/kg of sibutramine. The effect of sibutramine on protein intake was diet- and gender-specific. All doses of sibutramine decreased total food intake regardless of gender and diet group beginning at 6 h post administration. In conclusion, sibutramine affected macronutrient selection and emphasis on dietary recommendations, as well as appropriate dosage according to gender should be considered during therapy.     

Ontogeny of two-way avoidance in male and female rats

In Experiment I, 17-, 21-, 36-, 51-, 90-, and 200-day-old male and female rats were given a single session of 100 two-way avoidance (TWA) trials. In the 2nd experiment, males and females of these ages and 15 and 28 days of age that were obtained from a different source, weaned at a later age, and housed differently received TWA training. Results of both studies showed that avoidance of 15-, 17-, and 21-day-old rats is low, but avoidance increases from 21 to 51 days of age. Avoidance of 95- and 200-day-old animals was generally lower than 51-day-old rats. No significant gender differences appeared until 90 days of age; at this age avoidance of males was lower than females. In Experiment III, CS intensity was varied and the US intensity was lower than that used in Experiment I and II. Avoidance of 21- and 90-day-old rats was higher with a more intense CS, but 21-day-olds were still lower than adults. Avoidance of 17-day-old rats was not affected by CS intensity.     

Effects of vasopressin on female sexual behavior in male rats

Intracerebroventricular (i.c.v.) injection of an Arg-vasopressin (AVP) antagonist did not stimulate female sexual behavior in adult castrated male rats treated with ovarian hormone but stimulated this behavior in male rats which were castrated on the day of birth. It is suggested that neonatal androgen stimulation in the male rat offsets the influence of AVP on female sexual behavior in the adult.     

Undernutrition in early life: lasting effects on activity and social behavior of male and female rats.

The growth-retarded offspring of mother rats undernourished throughout pregnancy and lactation were fed ad libitum from weaning. Males were tested at 100 days of age, and ovariectomized females at 150 days. After 2 weeks of isolation, pairs of males consisting of 1 control (C) and 1 previously undernourished (PU) rat were observed for 10 min on each of 9 consecutive days. Similarly paired and treated female rats were tested a total of 8 times, the first 3 tests being separated from the last 5 by a 10-day interval. The PU rats, whether male or female, performed more rearing responses and PU male rats ambulated more in the social situation than C rats. The PU males also performed more of the social responses allogroom, walk over, and mount than C males. Similarly, PU females performed more allogroom and crawl under than C females. In general, PU rats were more active than C rats and more socially responsive.