The partner preference paradigm: a method to study sexual motivation and performance of female rats

Sexual behavior of the female rat consists of initiative, as well as receptive components. Previous studies on female sexual behavior have focused on the reflexive response to a male's mount, i.e., the lordosis reflex, whereas the initiative and soliciting gestures that are exhibited by the female during copulation were ignored by most researchers. This bias led to a misconception of the female's role in the sexual act, according to which the female is passive and submissive, whereas the male rat is sexually dominant or even aggressive. In this paper, we describe a procedure, the partner preference paradigm, designed to investigate and quantify sexual motivation, initiation and solicitation in female rats. In this paradigm, the female can control the sexual act because the mobility of her sexual partner is limited. This setting enables to measure a variety of soliciting behaviors that reflect the active seeking of sexual contact by an estrous female. In addition, this paradigm enables the evaluation of the females' motivation to engage in a sexual act, by measuring the preference for a sexually appropriate over an indifferent partner. Moreover, the partner preference paradigm may be easily adopted for studies in male subjects, allowing the comparison of males' and females' responses to various experimental conditions.Themes: Neural basis of behaviorTopics: Motivation and emotion; Hormonal control of reproductive behavior     

Evaluation of chronic alcohol self-administration by a 3-bottle choice paradigm in adult male rats. Effects on behavioural reactivity, spatial learning and reference memory

Chronic ethanol consumption is able to modify emotional behaviour and cognition in humans. In particular, the effects exerted by alcohol may depend on doses, time and modalities of administration. In this study we investigated, in adult male rats, ethanol self-administration and preference patterns using a 3-bottle choice paradigm with water, 10% ethanol solution, and white wine (10%, v/v), along a four-week period. The influence of alcohol free-access on novelty-induced explorative behaviour in the open field, and on spatial learning and reference memory in the Morris water maze was also evaluated. Our results indicate that: (i) rats show a higher preference for alcohol, in the first two weeks of the paradigm, displaying a higher consumption of 10% ethanol solution than white wine; in the last two weeks, they reduce their alcoholic preference, drinking the same moderate amounts of the two alcoholic beverages; (ii) at the fourth week of the free-access paradigm rats show a high explorative behaviour in the central squares of the open field and an improvement in spatial information processing in the new-place learning task of the Morris water maze. In conclusion our data suggest that, interestingly, rats exposed to the free-access paradigm were able to self-regulate their alcoholic intake, and indicated that a moderate alcohol consumption was able to induce an increase in behavioural reactivity and an enhancement in spatial learning flexibility.     

A cognitive rehabilitation paradigm effective in male rats lacks efficacy in female rats

Cognitive dysfunction, as a consequence of dementia, is a significant cause of morbidity lacking efficacious treatment. Females comprise at least half of this demographic but have been vastly underrepresented in preclinical studies. The current study addressed this gap by assessing the protective efficacy of physical exercise and cognitive activity on learning and memory outcomes in a rat model of vascular dementia. Forty ovariectomized Sprague-Dawley rats (∼6 months old) were exposed to either a diet high in saturated fats and refined sugars or standard laboratory chow and underwent either chronic bilateral carotid occlusion or Sham surgery. Learning and memory abilities were evaluated using standard cognitive outcomes over the ensuing 6 months, followed by histologic analyses of hippocampal CA1 neurons. In Experiment 1, we confirmed hypoperfusion-induced cognitive dysfunction using a 2 × 2 (Surgery × Diet) experimental design, without alterations in hippocampal architecture. In Experiment 2, hypoperfused animals were either exposed to alternating days of physical (wheel running) and cognitive activity (modified Hebb–Williams maze) or sedentary housing. In contrast to males, this combination rehabilitation paradigm did not improve cognition or histopathologic outcomes in hypoperfused animals. These findings, highlighting differences between female and male animals, show the necessity of including both sexes in preclinical experimentation.     

Long-lasting handling affects behavioural reactivity in adult rats of both sexes prenatally exposed to diazepam

Environmental stressors can substantially affect the adaptive response of rats to novelty in a sexually dimorphic manner. Gender-related differences are also observed in neurochemical and behavioural patterns of adult rats following prenatal exposure to diazepam (DZ). In the present study the behavioural reactivity to novelty is investigated in open field (OF) and in acoustic startle reflex (ASR) tests, in non handled (NH), short-lasting handled (SLH) and long-lasting handled (LLH) adult male and female rats prenatally exposed to DZ. A single daily s.c. injection of DZ (1.5 mg/kg) over gestation days 14-20 decreases GABA/BDZ receptor function in both sexes, as shown by the decreased electrographic hippocampal response to DZ and the increased response to picrotoxin, after intra-locus coeruleus injection of the two compounds. In OF NH DZ-exposed males display a lower total distance travelled (TDT), a higher rearing frequency (RF) and a greater number of transitions in the centre of the arena (CNT) compared to NH rats prenatally exposed to vehicle. Conversely, NH DZ-exposed females show slight changes in TDT and RF and a greater reduction in CNT and in the amount of time spent in the centre of the arena (CAT). These effects are associated with an increase in the peak amplitude of the ASR in both sexes. Short-lasting handling slightly influences DZ-evoked effects in animals of both sexes. In DZ-exposed males long-lasting handling attenuates the reduction in TDT and the enhancement in RF, prevents the increase in CNT and reduces the peak amplitude of ASR. In DZ-exposed females, long-lasting handling increases TDT and RF, induces a lower avoidance of the centre of the arena, and does not modify the peak amplitude of ASR, when compared to controls. These findings indicate that prenatal exposure to DZ differently affects behavioural reactivity in adult male and female rats, and suggest that a long-lasting handling is able to attenuate some behavioural deficits induced by prenatal DZ exposure.     

Circadian preference and cognitive functioning among rehabilitation inpatients

The influence of circadian preference was examined among 56 morning-oriented rehabilitation inpatients with cognitive (n=28) and noncognitive (n=28) impairments. Each individual was tested twice: morning (preferred time) and evening (nonpreferred time); sessions and test batteries were counterbalanced to control for practice effects. Standard measures assessed attention, language, memory, visuospatial, and executive functions. Persons with cognitive impairment showed disproportionate vulnerability to the effects of circadian preference and time of testing, performing more poorly at nonpreferred than preferred times. Substantial effects (eta2 .12 to .48) were found on tests of executive functioning and tasks incorporating similar higher-order demands (e/g/. complex figure copy). Results are supported by tympanic temperature changes during a vigilance task, and index of cerebral blood flow in response to cognitive challenge. Cognitive reserve theory is suggested as an explanation for the differential effects. These findings may have implications for inpatient therapeutic interventions and discharge planning.     

Handedness is associated with immune functioning and behavioural reactivity in rhesus macaques

In the present study we examined the relationship among handedness, immune functioning, and behavioural reactivity in rhesus macaques. We used the absolute number of CD4+ (T-helper) and CD8+ (T-suppressor) cells as dependent measures of immune functioning. We derived reactivity profiles from behavioural responses to a threat, and hand preference profiles from a quadrupedal food-reaching test. The results indicate positive correlations between the frequency of right versus left hand reaches and the absolute number of CD4+ cells, and between the frequency of right versus left hand reaches and the degree of human-directed aggression in response to an invasive threat. Immune measures were not associated with the strength of hand preference. These results are consistent with and extend previous findings obtained with rodents to nonhuman primates and provide further support for the view that behavioural lateralisation is associated with immune functioning and behavioural reactivity.     

Handedness is associated with immune functioning and behavioural reactivity in rhesus macaques

In the present study we examined the relationship among handedness, immune functioning, and behavioural reactivity in rhesus macaques. We used the absolute number of CD4+ (T-helper) and CD8+ (T-suppressor) cells as dependent measures of immune functioning. We derived reactivity profiles from behavioural responses to a threat, and hand preference profiles from a quadrupedal food-reaching test. The results indicate positive correlations between the frequency of right versus left hand reaches and the absolute number of CD4+ cells, and between the frequency of right versus left hand reaches and the degree of human-directed aggression in response to an invasive threat. Immune measures were not associated with the strength of hand preference. These results are consistent with and extend previous findings obtained with rodents to nonhuman primates and provide further support for the view that behavioural lateralisation is associated with immune functioning and behavioural reactivity.     

Psychiatric, psychosocial, and cognitive functioning of female adolescents with ADHD

OBJECTIVE: To characterize the psychiatric, psychosocial, and cognitive functioning of female adolescents with attention-deficit/hyperactivity disorder (ADHD) in comparison with female controls and males with ADHD. Female controls were also compared with male controls to verify gender differences in a nonclinical sample. METHOD: One hundred seven adolescents from Southern Ontario aged 13 to 16 were included: 24 females with ADHD, 35 males with ADHD, 28 control females, and 20 control males. All were assessed with semistructured interviews, questionnaires, and tests of achievement and intellectual functioning. RESULTS: After controlling for parental education and estimated Full Scale IQ, females with ADHD were more impaired than control females in depression, anxiety, distress, teacher relationships, stress, attributional styles, and locus of control and on all cognitive and achievement measures. Females with ADHD were more impaired than males with ADHD in self-reported anxiety, distress, depression, locus of control, and vocabulary scores. These group differences were confirmed by higher ratings by parents and teachers in symptoms of psychopathology. Males with ADHD were more impaired in processing speed. Some gender differences (locus of control and vocabulary scores) were eliminated when controlling for ADHD severity. The absence of any differences between male and female controls indicates gender differences were specific to the clinical groups. CONCLUSION: Females with ADHD are at high risk for more psychological impairment than both males with ADHD and control females. The identified psychosocial problems point to areas for intervention.     

Sex differences in salt preference and taste reactivity in rats

Previous studies have shown that female rats consume significantly more sodium chloride (NaCl) than do age-matched males. The gustatory contribution to this sex difference was examined in the following experiments. In Experiment 1, female rats demonstrated a higher two-bottle preference for NaCl ranging from 0.03 M to 1.0 M than did age-matched males. Next, to determine if the animal's sex modified gustatory sensitivity for NaCl, taste reactivity responses elicited by intraoral infusions (0.8 ml) of NaCl (0.03 M, 0.15 M, 0.3 M, and 1.0 M) were measured in age-matched male and female Sprague-Dawley rats. Intraoral infusions of NaCl were administered in ascending concentration order on successive days. During the intraoral infusion, the animal's oral motor taste reactivity responses were videotaped and subsequently analyzed to determine the number of ingestive and aversive responses. Intraoral infusions of 0.15 M and 0.3 M NaCl elicited reliably more ingestive responses and 1.0 M NaCl more aversive responses in females than in males. Because differences in taste reactivity were not found for all those concentrations for which female rats showed a higher preference than did males, changes in gustatory sensitivity contributes to, but does not appear to fully account for the female rats' preference for NaCl.     

Subjective preference for lamotrigine or topiramate in healthy volunteers: relationship to cognitive and behavioral functioning

OBJECTIVE: Outcomes research emphasizes patient self-assessment and preferences in optimizing treatment. We previously showed that lamotrigine produces significantly less cognitive and behavioral impairment compared with topiramate. In the current study we extend these observations to subject self-report of preference for lamotrigine or topiramate independent of potentially confounding effects of seizures or seizure control. Additionally, drug preference was related to effects of lamotrigine and topiramate on objective neuropsychological tests as well as self-perception on behavioral instruments. METHODS: Thirty-seven healthy volunteers completed a double-blind, randomized crossover design incorporating two 12-week treatment periods of lamotrigine and topiramate each titrated to a dose of 300 mg/day. Evaluation of 23 objective neuropsychological and 15 subjective behavioral measures occurred at four times: pretreatment baseline, first treatment, second treatment, and posttreatment baseline. Preference for lamotrigine or topiramate was assessed, while blinding was maintained, at the final study visit when each subject was asked which drug he or she would prefer to take. RESULTS: A large majority (70%) preferred lamotrigine, 16% stated preference for topiramate, and 14% had no preference (drugs equivalent). Consistent with preference, those preferring lamotrigine performed better on 19 of 23 objective and 13 of 15 subjective behavioral measurements while on lamotrigine. Inconsistent with preference, subjects preferring topiramate performed better on 19 of 23 objective and 9 of 15 subjective behavioral measures while on lamotrigine. Topiramate preference also did not correlate with IQ, serum concentration, body mass index, age, or gender. Topiramate preference did relate to responses on the Profile of Mood States. CONCLUSION: Lamotrigine was preferred by the majority of subjects, congruent with objective neuropsychological and subjective behavioral measures. In contrast, for those stating a preference for topiramate the results on objective neuropsychological measures were impaired while fewer complaints were noted on the Profile of Mood States. This suggests that preference for topiramate may be determined by an effect on mood.     

Status epilepticus in immature rats leads to behavioural and cognitive impairment and epileptogenesis

It remains under dispute whether status epilepticus (SE) in the perinatal period or early childhood or the underlying neuropathology is the cause of functional impairment later in life. The present study examined whether SE induced by LiCl-pilocarpine in normal immature brain (at the age of 12 or 25 days; P12 or P25) causes cognitive decline and epileptogenesis, and the data were compared to those of rats undergoing SE as adults. Rats in the P12 group had impaired memory (repeated exposure to open-field paradigm) and emotional behaviour (lower proportion of open-arm entries and higher incidence of risk assessment period in elevated plus-maze) when assessed 3 months after SE, although not as severe as in the older age groups. Importantly, video-electroencephalography monitoring 3 months after SE demonstrated that 25% of rats in the P12 and 50% in P25 group developed spontaneous seizures. Only nonconvulsive seizures (ictal activity in hippocampus accompanied by automatisms) were recorded in the P12 group whereas rats in the P25 group exhibited clonic convulsions. The present findings indicate that SE is harmful to the immature brain as early as P12, which might be compared with early infancy in humans.     

17Beta-oestradiol modulates glucocorticoid, neural and behavioural adaptations to repeated restraint stress in female rats

Sex steroids have a role in modulating responses that extends beyond reproduction. The current study investigated the influence of the sex steroid 17beta-oestradiol on hypothalamic-pituitary-adrenal (HPA) and behavioural responses to acute or repeated restraint stress. Ovariectomized rats treated with 17beta-oestradiol or peanut oil via a subcutaneous silastic capsule were subjected to daily handling (non stressed), acute (single, 1 h) or daily (10 days, 1 h/day) restraint stress. Blood collected at the end of stress revealed that 17beta-oestradiol treatment augmented the corticosterone response to acute restraint. After daily exposure to restraint, the corticosterone response was noticeably diminished in untreated females but 17beta-oestradiol-treated rats still showed an exaggerated response compared to castrated, untreated females. Brain tissue collected 3 h after the end of restraint was probed using isotopic in situ hybridization for corticotropin-releasing factor (CRF) and vasopressin gene expression in the paraventricular nucleus (PVN) of the hypothalamus. 17beta-oestradiol treatment at the higher dose (120 microg/ml) decreased basal CRF mRNA. Stress caused an increase in CRF mRNA expression in 17beta-oestradiol-treated rats but not in the vehicle group. Repeated restraint stress caused an increase in PVN parvocellular vasopressin gene expression, which was more pronounced in 17beta-oestradiol-replaced rats. Animals were exposed to the elevated plus maze for 5 min as a test for anxiety. Non-stressed control rats with or without 17beta-oestradiol replacement spent the same percentage amount of time exploring the open arms of the maze. Previous exposure to acute restraint stress caused a marked reduction in the time spent exploring the open arms, indicating an increase in anxiety levels in these rats; this effect was observed in both vehicle and 17beta-oestradiol-treated rats. After repeated restraint stress, 17beta-oestradiol-replaced rats spent as much time exploring the open arms of the maze as controls, indicating adaptation. By contrast, nonreplaced rats were still showing a significant reduction in open arm exploration after repeated restraint. The present study presents novel data showing that the HPA axis remains reactive to repeated stress in 17beta-oestradiol-treated ovariectomized rats, but stress-induced anxiety behaviour is reduced.     

Effects of nucleus accumbens lesion on female rat sexual receptivity and proceptivity in a partner preference paradigm

A partner preference paradigm, stud male vs estrous female, was used to study sexual behavior. Ovariectomized Wistar rats received bilateral electrolytic (n = 33) or sham (n = 16) lesion of the nucleus accumbens. Animals were tested in two different experimental situations, either with stimulus animals tethered (test with possibility of mating) or with stimulus animals behind a wire mesh (test without possibility of mating). Each test was carried out once prior to surgery and twice postoperatively following priming with estradiol benzoate and progesterone. Lordosis, rejection behaviors and soliciting patterns were scored in tests with tethered stimulus animals. The tendency of the experimental female to approach and remain in the vicinity of each stimulus animal was quantified to study the partner preference. Nucleus accumbens lesion increased the number of rejection responses to male mount attempts without modifying either receptivity estimated by lordosis reflex or soliciting behaviors. Control females showed a statistically significant preference for the male throughout the experiments. Lesioned females exhibit a preference for the male only in the test without sexual interaction possibility. This preference disappeared in the test with possibility of mating and it was even reversed when the male showed copulatory activity. These results, together with the absence of changes in lordosis behavior and soliciting activity, suggest that both the inversion in preference and the higher levels of mount rejections found in the lesioned animals are more likely attributable to hyperreactivity to the copulatory stimulus rather than an alteration in the female's rat sexual motivation.     

Premorbid functioning, cognitive functioning, symptoms and outcome in schizophrenia.

In this study we examined the relationship between premorbid functioning, outcome, cognitive functioning and positive and negative symptoms of schizophrenia. Cognitive functioning and symptoms were examined longitudinally in a sample of 39 subjects with schizophrenia (according to the DSM-III criteria). Subjects were assessed at admission to hospital and six months later during a period of relative remission. Premorbid functioning was significantly associated with negative symptoms but not with positive symptoms at both the acute phase and the remitted phase of the illness. Outcome was also associated with negative symptoms at admission and with both positive and negative symptoms at follow-up. Deficits on cognitive tests of verbal reasoning and concept formation were significantly associated with poor premorbid functioning and outcome.     

Anxiety-like behavior and cognitive flexibility in adult rats perinatally exposed to increased serotonin concentrations

Serotonin (5-hydroxytryptamine, 5HT) is a biologically active amine that regulates the development of 5HT neurons and target tissues during neurogenesis, while later it assumes the function of a neurotransmitter. Serotonin mediates many essential behaviors common to all mammals, and is held responsible for anxiety-like behavior and cognitive rigidity. Proper serotonin levels, controlled through 5HT synthesis and metabolism, are crucial for normal brain development. In this study we investigated anxiety-like behavior and cognitive flexibility in adult animals after exposing their developing brains to increased 5HT concentrations. Wistar rats were treated subcutaneously from gestational day 12 to post-natal day 21 with the immediate 5HT precursor 5-hydroxytryptophan (5HTP, 25mg/kg), a non-selective MAO inhibitor tranylcypromine (TCP, 2mg/kg), or saline. After reaching adulthood, animals were tested for anxiety-like behavior (exploratory behavior, thigmotactic behavior, social contact, and reaction to stressful stimulus) and cognitive flexibility (ability for reversal learning). Results of the behavioral studies corresponded with our previous neurochemical findings. Treatment with 5HTP, which has induced mild reduction in cortical 5HT concentrations, caused reduction in only one aspect of anxiety-like behavior (increased exploratory activity). Treatment with TCP, which lead to drastic reduction in 5HT concentration/function, resulted in a highly anxiolytic phenotype (reduced thigmotaxis, reaction to stress, and social anxiety) with improved cognitive flexibility. Although further neurochemical, anatomical and gene-expression studies are needed to elucidate the mechanisms underlying the observed behavior, we hope that our results will contribute to the understanding of the role of serotonin in anxiety-like behavior and cognitive rigidity.     

Prenatal stress affects behavioral reactivity to an intense stress in adult female rats

In rats, prenatal stress has been shown to influence behavioral and neuroendocrinological immediate responsivity to several kinds of mild stress in adulthood. Indeed, prenatal stress increases anxiety-like behavior, depressive-like disturbances and alters the hypothalamo-pituitary-adrenal (HPA) axis response to stress. However, long-term effects of an intense stress on behavior of prenatally stressed rats remain unknown. Moreover, most studies focus on male offspring. The aim of our study was to evaluate long-term behavioral effects of an aversive procedure consisting of an intense footshock (2 mA, 10 s) followed by three weekly situational reminders in prenatally stressed female rats. Prenatal stress was achieved by restraining the pregnant dams under bright light three times per day for 45 min during the last week of pregnancy. The aversive procedure induced long-term behavioral alterations in adult animals: an increase of immobility in the footshock chamber, hypoactivity in a novel environment and decreased avoidance of an "aversive-like" context. Interestingly, the procedure induced opposite effects in control and prenatally stressed females, suggesting bi-directional manifestation in some situations. In conclusion, prenatal stress affects behavioral response to an intense footshock associated with repeated situational reminders. These results suggest that early stress may interact with later ability to cope with intense stress in adulthood.