Comparison of the antidepressant sertraline on differential depression-like behaviors elicited by restraint stress and repeated corticosterone administration.

Depressive disorder involves emotional, cognitive, autonomic and endocrine alterations and also evidences support the role of stress in the development of this disorder. Because the hypothalamic-pituitary-adrenal axis is involved in the stress response with a concomitant rise in plasma corticoids, the present study compares the antidepressant effects of sertraline (10mg/kg, i.p.) on behavioral changes elicited by (i) restraint stress (2.5h/day for 13days) and (ii) corticosterone injections (30mg/kg, s.c., for 13days). Stressed animals, but not corticosterone-treated animals displayed anxiety behavior and a reduction in the acquisition of a conditioned avoidance response to 25% of control levels (8.0±2.2 vs. 31.7±3.2), being this effect partly sensitive to sertraline. Stressed, but not corticosterone-treated, animals displayed an increased escape failure compared with the control group (24.6%±3.5 vs. 1.6±0.7), an effect partly prevented by sertraline treatment (7.3%±2.0). Both stressed rats and corticosterone-treated rats showed an increase in immobility in the forced swim test, an effect prevented by sertraline. These results suggest that the altered behaviors elicited by stress and corticosterone can be explained by neural modifications that are sensitive to the sertraline antidepressant.

Chronic fluoxetine treatment induces structural plasticity and selective changes in glutamate receptor subunits in the rat cerebral cortex.

It has been postulated that chronic administration of antidepressant drugs induces delayed structural and molecular adaptations at glutamatergic forebrain synapses that might underlie mood improvement. To gain further insight into these changes in the cerebral cortex, rats were treated with fluoxetine (flx) for 4 weeks. These animals showed decreased anxiety and learned helplessness. N-methyl-d-aspartate (NMDA) and alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA) receptor subunit levels (NR1, NR2A, NR2B, GluR1 and GluR2) were analysed in the forebrain by both western blot of homogenates and immunohistochemistry. Both methods demonstrated an upregulation of NR2A, GluR1 and GluR2 that was especially significant in the retrosplenial granular b cortex (RSGb). However, when analysing subunit content in postsynaptic densities and synaptic membranes, we found increases of NR2A and GluR2 but not GluR1. Instead, GluR1 was augmented in a microsomal fraction containing intracellular membranes. NR1 and GluR2 were co-immunoprecipitated from postsynaptic densities and synaptic membranes. In the immunoprecipitates, NR2A was increased while GluR1 was decreased supporting a change in receptor stoichiometry. The changes of subunit levels were associated with an upregulation of dendritic spine density and of large, mushroom-type spines. These molecular and structural adaptations might be involved in neuronal network stabilization following long-term flx treatment.

Estilos de aprendizaje de estudiantes de medicinaen universidades latinoamericanas y españolas: relación con los contextos geográficos y curriculares / Medical students learning styles in Latin American and Spanish universities: relation with geographical and curricular contexts

Objetivo. Determinar si los estilos de aprendizaje (EA)de los estudiantes de medicina se correlacionan con el contexto geográfico, con el contexto curricular o con el nivel de la carrera. Sujetos y métodos. El estudio se realizó en 490 estudiantes de las Escuelas de Medicina de las Universidades de Chile (Santiago, Chile), Nacional de Cuyo (Mendoza, Argentina), San Francisco Xavier (Sucre,Bolivia), Zaragoza y País Vasco (España). Se aplicó el cuestionario Honey-Alonso, que valora la preferencia por cada uno de cuatro EA: activo, reflexivo, teórico y pragmático. También se evaluó el EA de acuerdo al modelo de Kolb. Resultados. Al relacionar el EA con el contexto geográficos observó que mientras los estudiantes de universidades españolas muestran un estilo preferentemente asimilador, siguiendo la denominación de Kolb, para Chile fue el acomodador y para Bolivia los estudiantes se distribuyen entre los estilos asimilador y divergente. Al comparar la distribución de los EA durante el tercer curso de medicina en dos facultades que poseen diferente currículo, no se observaron diferencias significativas. Los EA en una Facultad de Medicina con un currículo basado en asignaturas(Chile) no mostraron diferencias en los tres cursos del estudio(1.º, 3.º y 5.º), siendo preferentes los estilos reflexivo y teórico. Conclusiones. El estudio permitió establecer diferencias significativas entre los estilos de aprendizaje de los estudiantes de Medicina en relación con el contexto geográfico, más que con los diferentes currículos, o a lo largo de los distintos cursos de la carrera (AU)

Aim. To establish a correlation between medical student learning styles (LS) and the geographical context, the curricular context and different academic levels. Subjects and methods. The study was performed in 490 undergraduate students from Medical Schools of the Universities of Chile (Santiago, Chile),Nacional de Cuyo (Mendoza, Argentina), San Francisco Xavier(Sucre, Bolivia), Zaragoza and País Vasco (Spain). The instrument used was the Honey-Alonso learning style questionnaire that assesses the student preference for one of four LS: active, reflexive, theoretic and pragmatic. In addition, LS according to the Kolb inventory were also assessed. Results. Using the Kolb inventory, significant differences were found when the LS were correlated with the geographical context. While Spanish students showed a high preference for the assimilator style of learning, Chilean students resulted to be mainly accommodators, and Bolivian students were both assimilators and divergent. Comparing the LS distribution during the third course in two universities with different curricula (problem and lecture based learning), there were no significant differences. LS of medical students from a Medical School with a lecture based curriculum (University of Chile) were not significantly different during the first, the third and the fifth level of their undergraduate students. They showed a significant preference for reflexive and theoretic styles of learning. Conclusions. The present study allowed demonstrating that significant differences among the styles of learning of medical students correlated with the geographical context more than with the different curricula, or along the different courses of the career (AU)

The hydroalcoholic extract of Salvia elegans induces anxiolytic- and antidepressant-like effects in rats.

Behavioral effects of a hydroalcoholic (60% ethanol) extract from the leaves of Salvia elegans Vahl (Lamiaceae) were studied in male Sprague-Dawley rats. The extract was administered intraperitoneally and its effects on spontaneous motor activity (total motility, locomotion, rearing and grooming behavior) were monitored. Putative anxiolytic and antidepressant properties of Salvia elegans were studied in the elevated plus-maze test (EPM) and in the forced swimming test (FST), respectively. Deleterious effects of Salvia elegans on learning and memory were also studied by using active and passive avoidance paradigms. The results revealed that all doses (3.12, 12.5, 25 and 50 mg/kg) of the extract caused a significant decrease in total motility, locomotion, rearing and grooming behavior. Only the dose of 12.5 mg/kg increased the exploration of the EPM open arms in a similar way to that of diazepam (1 mg/kg). In the FST, all doses of the extract induced a reduction of immobility, in a similar way to that of fluoxetine (10 mg/kg) and imipramine (12.5 mg/kg), along with a significant increase in the time spent in swimming behavior. Acquisition of active avoidance responses was disrupted by pre-treatment with the extract, but retention of a passive avoidance response was not significantly modified. These results suggest that some of the components of the hydroalcoholic extract of Salvia elegans have psychotropic properties, which deserve further investigation.

Anxiolytic and antidepressant-like effects of the hydroalcoholic extract from Aloysia polystachya in rats.

Behavioral effects of a hydroalcoholic extract from leaves of Aloysia polystachya (Griseb.) Moldenke (Verbenaceae) were studied in female Sprague-Dawley rats. The extract was administered intraperitoneally and its effects on spontaneous motor activity (total motility, locomotion, rearing and grooming behavior) were monitored. Anxiolytic-like properties were studied in the elevated plus-maze (EPM) test and the possible antidepressant-like actions were evaluated in the forced swimming test (FST). The results revealed that high doses of the extract (25 and 50 mg/kg, i.p.) caused a significant decrease in total motility, locomotion, rearing and grooming behavior. All doses injected (from 1.56 to 50 mg/kg) increased the exploration of the EPM open arms in a similar way to that of diazepam (1 mg/kg, i.p.). In the FST, the extract (12.5, 25 and 50 mg/kg) was as effective as fluoxetine (10 mg/kg, i.p.) and imipramine (12.5 mg/kg, i.p.) in reducing immobility, along with a significant increase in swimming and climbing, respectively. These results suggest that some of the components of the hydroalcoholic extract of A. polystachya, such as thujone and carvone among others, may have sedative, anxiolytic and antidepressant-like properties which deserve further investigation.

Chronic stress impairs acoustic conditioning more than visual conditioning in rats: morphological and behavioural evidence.

Chronic stress affects brain areas involved in learning and emotional responses. These alterations have been related with the development of cognitive deficits in major depression. The aim of this study was to determine the effect of chronic immobilization stress on the auditory and visual mesencephalic regions in the rat brain. We analyzed in Golgi preparations whether stress impairs the neuronal morphology of the inferior (auditory processing) and superior colliculi (visual processing). Afterward, we examined the effect of stress on acoustic and visual conditioning using an avoidance conditioning test. We found that stress induced dendritic atrophy in inferior colliculus neurons and did not affect neuronal morphology in the superior colliculus. Furthermore, stressed rats showed a stronger impairment in acoustic conditioning than in visual conditioning. Fifteen days post-stress the inferior colliculus neurons completely restored their dendritic structure, showing a high level of neural plasticity that is correlated with an improvement in acoustic learning. These results suggest that chronic stress has more deleterious effects in the subcortical auditory system than in the visual system and may affect the aversive system and fear-like behaviors. Our study opens a new approach to understand the pathophysiology of stress and stress-related disorders such as major depression.

Central nervous system activity of the hydroalcoholic extract of Casimiroa edulis in rats and mice.

In order to evaluate the effects produced by the hydroalcoholic extract of leaves from Casimiroa edulis on the central nervous system, different behavioral tests and animal models of depression and anxiety were performed. The extract was administered intraperitoneally in male and female rats and tested on spontaneous motor activity, locomotor activity, exploration of an elevated plus-maze (EPM) and in the forced swimming test (FST). In addition, the extract was administered orally in male and female mice and evaluated in the following tests: general observation, pentobarbital-induced hypnosis, EPM, rota-rod, hole-board, and marble-burying. The results revealed that, in rats, the extract caused considerable reduction of locomotor and exploratory activities and increased the exploration of the EPM open arms in a similar way that diazepam. In the FST, the extract was as effective as fluoxetine in inducing shortening of immobility, along with a significant increase on climbing duration. On the other hand, in mice, the extract prolonged pentobarbital-induced hypnosis, increased exploration of the EPM open arms and partially protected from the pentylenetetrazol-induced convulsions. No significant effect was evident on motor coordination, hole-board and marble-burying tests. These results suggest that the hydroalcoholic extract of Casimiroa edulis may contain sedative principles with potential anxiolytic and antidepressant properties, which need further investigation.

Inhibition of DT-diaphorase potentiates the in vivo neurotoxic effect of intranigral injection of salsolinol in rats.

The present study shows that intranigral injection of dicoumarol, a DT-diaphorase inhibitor, potentiates the neurotoxic effect of salsolinol (salsolinol 1.25 nmoles plus dicoumarol 2 nmoles; in 2 microl). Rats treated with dicoumarol plus salsolinol presented a characteristic contralateral rotational behaviour when they were stimulated with apomorphine (0.5 mg/kg, s.c.), similar to rats injected unilaterally with 6-hydroxydopamine (6-OHDA). These rats also exhibited impairment of motor and cognitive behaviours. The results support the hypothesis that DT-diaphorase plays a protective role in the nigrostriatal dopaminergic systems.

Behavioral effects of aminochrome and dopachrome injected in the rat substantia nigra.

The exact mechanism of cell death in neurodegenerative diseases remains obscure, although there is evidence that their pathogenesis may involve the formation of free radicals originating from the oxidative metabolism of catecholamines. The purpose of this study was to evaluate the degree of neurodegenerative changes and behavioral impairments induced by unilateral injection into the rat substantia nigra of cyclized o-quinones, aminochrome and dopachrome, derived from oxidizing dopamine and L-DOPA, respectively, with Mn(3+)-pyrophosphate complex. The behavioral changes were compared with those induced after selective lesions of dopaminergic neurons with 6-hydroxydopamine (6-OHDA). Intranigral injection of aminochrome and dopachrome produced impairment in motor and cognitive behaviors. The behavioral impairment was also revealed by apomorphine-induced rotational asymmetry. Apomorphine (0.5 mg/kg sc) significantly increased rotational behavior in rats injected with aminochrome and dopachrome. These rats presented a clear motor bias showing a significant contralateral rotation activity, similar but less vigorous that in rats injected with 6-OHDA. The avoidance conditioning was seriously impaired in rats injected with aminochrome and dopachrome although only dopachrome-injected rats showed a similar hypomotility to 6-OHDA-injected rats. The behavioral effects were correlated to the extent of striatal tyrosine hydroxylase (TH)-positive fiber loss. Rats receiving unilateral intranigral aminochrome and dopachrome injections exhibited a 47.9+/-5.1% and a 39.7+/-4.4% reduction in nigrostriatal TH-positive fiber density. In conclusion, this study provided evidence that oxidizing DA and L-DOPA to cytotoxic quinones, aminochrome and dopachrome appears to be an important mediator of oxidative damage in vivo.

Inhibition of DT-diaphorase is a requirement for Mn(III) to produce a 6-OH-dopamine like rotational behaviour.

Intracerebral manganese administration together with the DT-diaphorase inhibitor dicoumarol [Mn(III) 40 nmol + -dicoumarol 2 nmol; in 4 micro l] into the left medial forebrain bundle (MFB) produced a behavioural pattern characterized by contralateral behaviour when the rats were stimulated with apomorphine (0.5 mg/kg s.c.), in a manner similar to that when administered to unilaterally 6-hydroxy-dopamine-lesioned animals. The same animals rotated towards the opposite side (ipsilaterally) when stimulated with d-amphetamine (2 mg/kg s.c.). These results support the idea that DT-diaphorase plays a protective role in the dopaminergic systems.

Gender, estrous cycle, ovariectomy, and ovarian hormones influence the effects of diazepam on avoidance conditioning in rats.

This study examines whether the hormonal condition of the rat modifies the effects of diazepam (0.25 and 1.0 mg/kg) on avoidance conditioning and other behavioral responses. Acquisition of a conditioning avoidance response (CAR) and spontaneous motor behaviors were assessed in intact male, in intact diestrous and estrous females, and in ovariectomized (OVX) rats injected with estradiol (2 microg/rat, SC) or progesterone (5 mg/rat, SC). A higher dose (1.0 mg/kg) of diazepam significantly impaired the acquisition of CARs in diestrous, OVX, OVX + progesterone, and male rats. Conversely, both doses of diazepam significantly improved the acquisition of CAR in estrous rats and in OVX rats injected with estradiol. These effects on conditioning avoidance were not accompanied with equivalent changes in spontaneous motor behaviors. Motor activity and grooming behavior decreased in all experimental groups after administration of 1.0 mg/kg of diazepam. On the contrary, diazepam 0.25 mg/kg increased motor activity in estrous, OVX + estradiol, and OVX + progesterone rats after, whereas grooming behavior was not affected in any group. These findings suggest a physiological influence of ovarian steroid hormones in modifying the benzodiazepine effects on conditioning avoidance and motor activity. The results are discussed considering that ovarian steroids may interact with diazepam on the GABA(A)/benzodiazapine/chloride ionophore complex, modifying the coupling between benzodiazepine sites and GABA(A) receptors.

Behavioral effects of dopamine agonists and antagonists: influence of estrous cycle, ovariectomy, and estrogen replacement in rats.

The influence of the hormonal condition on the reactivity of central dopamine (DA) receptors was studied in male and in intact and ovariectomized (OVX) female rats. They were injected with selective DA agonists, acting either on D1 (SKF 38393, 2.5 or 10 mg/kg) or D2 receptors (PPHT, 31.3 or 125 microg/kg), or with selective DA antagonists, acting either on D1 (SCH 23390, 6.25 or 25 microg/kg), or D2 receptors (sulpiride, 10 or 40 mg/kg). The acquisition of an avoidance conditioning response (CAR) and the performance of some spontaneous motor behaviors were tested. Both D1 and D2 agonists and antagonists impaired the acquisition of CARs in diestrous, OVX, and male rats. Nevertheless, the effects of these drugs during estrus and in estradiol-primed OVX rats were different according to the drug and the dose injected. Whereas SKF 38393 failed to induce significative changes, PPHT and low doses of SCH 23390 and sulpiride improved the acquisition of CARS in those groups. The effects on conditioning were not accompanied with equivalent changes in spontaneous motor activity. Estradiol level fluctuations that occur in female rats within the estrous cycle or in OVX rats primed with estradiol would be responsive of changes in the response to DA agents. Although the reactivity of central DA systems is differentially affected by the hormonal condition of the rat, the precise mechanism of this modulatory action remains unknown.

Effects of LHRH on avoidance conditioning in normally cycling and ovariectomized female rats.

Several studies have demonstrated that the peptide LHRH can modify behavior in the male rat. Peripheral and intracerebral infusions of LHRH impair the acquisition of conditioned avoidance responses (CARs) and increase some spontaneous motor behaviors, such as head shaking and grooming. The present study was undertaken to detect the effects of LHRH on the acquisition of CARs and spontaneous motility in normally cycling and ovariectomized (OVX) Sprague-Dawley female rats. Normally cycling females were separated in four groups, according to the stage of the estrous cycle. Ovariectomized female rats were pretreated, 48 h before the experiment, with estradiol benzoate (10 microg/kg) or corn oil. LHRH (6.25, 25, or 50 microg/kg) was subcutaneously injected and the behavioral tests began 1 h after. Low doses of LHRH stimulated the acquisition of CARs during proestrus, estrus, and metestrus, whereas higher doses impaired conditioning in all the four stages of the cycle. High doses of LHRH impaired acquisition in OVX rats treated with oil and potentiated the depressant effects of EB on this behavior. The effects of LHRH on spontaneous motor activity were either stimulatory or inhibitory, according to the hormonal status and the dose administered. High doses of LHRH decreased motor responses in the diestrous rat. All the doses of LHRH increased the number of headshakes during proestrus, estrus, and metestrus, while the other motor responses were scarcely or not affected by LHRH in these stages. In OVX rats LHRH increased rearing, head shaking, and grooming behavior. These results support a role of LHRH in the modulation of conditioned and spontaneous behavior. They could provide an explanation to the behavioral changes observed across the estrous cycle and those observed after EB priming in OVX rats.

Ketanserin and anxiety levels: influence of gender, estrous cycle, ovariectomy and ovarian hormones in female rats.

The influence of gender, estrous cycle, ovariectomy and ovarian hormones on the behavioral effects of the 5-HT2 receptor antagonist, ketanserin (KET), was studied. Intact males, female rats in the four stages of the estrous cycle and ovariectomized (OVX) female rats 14 days after surgery were used. The OVX rats received progesterone [PROG, 25 mg/kg, subcutaneously (SC)] and/or estradiol benzoate (EB, 10 micrograms/kg, SC). KET (3 mg/kg, SC) was injected 30 min before testing. All the animals were subjected to the following behavioral tests: exploration of an elevated plus-maze and retention of a passive-avoidance response. KET enhanced the exploration of the open arms in diestrous female rats but inhibited this behavior during the other stages of the cycle and in OVX rats injected either with oil or EB. This dose of KET was ineffective in males and in OVX rats injected with PROG. Furthermore, KET inhibited the retention of the passive avoidance response in males, in diestrous and metestrous female rats and in OVX rats injected with oil. In estrous females and in OVX rats injected with EB, KET enhanced the passive-avoidance response. These results demonstrate that the sensitivity to KET differs with the gender, estrous cycle and hormonal treatment and suggest that central serotonergic activity is influenced by the hormonal status of the animal.

Ketanserin effects on rat behavioral responses: modifications by the estrous cycle, ovariectomy and estradiol replacement.

The present investigation was designed to explore the influence of estrous cycle phase, ovariectomy, and estradiol replacement on the behavioral effects of the 5-HT2 receptor antagonist, ketanserin. The parameters under investigation were ketanserin-influenced acquisition of conditioning avoidance responses (CARs), and the performance of some spontaneous motor behaviors. Ketanserin (KET 3 mg/kg) injected subcutaneously 30 min before testing improved active conditioned avoidance in intact female rats at estrus, and in ovariectomized (OVX) rats with estradiol replacement. Furthermore, KET impaired performance in female rats at diestrus and after ovariectomy. In male rats, which were included in this study in order to compare their behavioral responses with those exhibited by female rats, KET administration enhanced acquisition of CARs. These results provide behavioral evidence for the hypothesis that central serotonergic activity is a function of the hormonal status of the animal. An additional segment of the present study focussed on motoric behaviors. Spontaneous motor activity, number of rears, and time spent in grooming behavior were significantly increased by KET in all groups studied. In contrast, blockade of 5-HT2 receptors failed to induce significant changes in the number of head shakes. Relationships between ovarian hormones and the central serotonergic system are discussed.

Effects of the estrous cycle and ovarian hormones on behavioral indices of anxiety in female rats.

The influence of the estrous cycle and the effects of exogenous administration of estradiol and progesterone on level of anxiety were studied in intact and ovariectomized rats. Intact Sprague-Dawley female rats were classified according to the stages of estrous cycle. Another group of rats was ovariectomized bilaterally and, 14 days after surgery, they received estradiol benzoate (10 micrograms/kg, s.c.) and/or progesterone (25 mg/kg, s.c.) or corn oil (1 ml/kg). The behavioral tests began 3 h after estradiol or 6 h after progesterone and consisted of: (1) exploration of an elevated plus-maze; and (2) retention of a passive avoidance response. Open-arm exploration of the plus-maze varied according to light intensity and the stages of the estrous cycle. There was a slight increase in open-arm exploration by rats in metestrus, under high light intensity. Low light intensity increased the exploration of the open arms by rats in proestrus and estrus, compared to the other phases of the cycle. Retention of the passive avoidance response was inhibited during proestrus and estrus. Progesterone increased open-arm exploration of the plus-maze under high light conditions, whereas estradiol antagonized this effect. Retention of passive avoidance was inhibited after estradiol or progesterone injection. These results suggest that the behavioral indices of anxiety can vary across the estrous cycle, that low light intensities have anxiolytic-like effects, and that the sensitivity to this effect is higher during proestrus and estrus. This could be explained through modulatory effects of ovarian hormones upon behavioral indices of anxiety.

Effect of oxotremorine on the acquisition of a conditioned avoidance response is modified by the estrous cycle, ovariectomy, and estradiol replacement in rats.

This study was designed to evaluate the influence of the hormonal status of the rat on the effects of a potent reversible muscarinic agonist, oxotremorine, on the acquisition of conditioning avoidance responses (CARs) and the performance of some spontaneous motor behaviors. Oxotremorine (OXO 50 and 100 micrograms/kg, intraperitoneally) given 5 min before testing improved active conditioned avoidance in intact female rats at estrus and in ovariectomized rats after estradiol replacement, and impaired performance in female rats at diestrus and after ovariectomy without estradiol replacement. No significant differences due to hormonal status of the rat in some spontaneous motor behaviors were observed. In fact, OXO in this dose range failed to induce significant changes in spontaneous motor activity, the number of rears diminished, and the time spent in grooming behavior increased in all groups studied. These results provided behavioral evidence for the hypothesis that central cholinergic activity is function of the hormonal status of the animal. Relationships between ovarian hormones and cholinergic system are discussed.

Influence of the estrous cycle and estradiol on the behavioral effects of amphetamine and apomorphine in rats.

This experiment was designed to investigate the influence of hormonal status of the rat on the effects of two doses of an indirect-acting dopamine agonist (amphetamine 0.25 and 1.0 mg/kg, IP) and a direct-acting dopamine agonist (apomorphine 62.5 and 250 micrograms/kg, SC) on the acquisition of conditioning avoidance responses (CARs) and the performance of some spontaneous behaviors. Active conditioned avoidance was improved by amphetamine in all the groups except in females at diestrus; apomorphine improved this response only in females at estrus and in ovariectomized rats after estradiol replacement, but the avoidance response was deteriorated in males and females at diestrus and after ovariectomy without estradiol replacement. Both dopaminergic drugs had contrasting effects on motor activity, number of rearings, and number of head shakes according to the hormonal status of the rat. Only the time spent in grooming behavior decreased after the treatment with both dopamine agonists in all of the five groups studied. These results provided behavioral evidence for the hypothesis that dopaminergic activity in the CNS is affected distinctively by modifications in the sexual hormone status (gender, estrous cycle, ovariectomy, and estradiol replacement). Relationships between ovarian hormones and dopaminergic system are discussed.

Progesterone effects on the acquisition of conditioned avoidance responses an other motoric behaviors in intact and ovariectomized rats.

This study demonstrates a significant impairment in the acquisition of conditioned avoidance responses in female rats during their estrus phase. Progesterone (PROG 5 mg) injected 6 h prior to the test, significantly enhanced the performance exhibited by rats at estrus, but not at diestrus. In ovariectomized rats, the acquisition of conditioned avoidance responses was similar to the exhibited during diestrus and this behavior was depressed by a single dose of estradiol benzoate (EB 2 micrograms) injected 48 h prior to the test. PROG antagonized the avoidance depression induced by EB, but it was not able to induce changes in the acquisition of conditioned avoidance response in ovariectomized rats without EB pretreatment. Estradiol appears to be the principal ovarian steroid modulating the acquisition of an avoidance task, whereas PROG seems to have a secondary role in this behavior, regulating the actions of estradiol on the brain. PROG failed to induce consistent changes in some spontaneous motor behaviors in intact and ovariectomized rats.

Behavioral effects of a LHRH antagonist in intact and ovariectomized rats.

The effects of the LHRH antagonism on the acquisition of conditioned responses (CARs) and spontaneous motility were studied in intact and ovariectomized rats. A synthetic antagonist of LHRH, [N-acetyl-D-p-chloro-Phe1,2,D-Trp3,D-Arg6,D-Ala10]-LHRH, was injected in a single dose (10 micrograms/rat, SC) at noon on the day of proestrus in the normally cycling rat, and behavioral experiments were carried out on the morning of estrus or metestrus. Two procedures were followed in the ovariectomized rats: in the first, the antagonist was injected 1 h before estradiol, and in the second, at noon on the day after estradiol replacement. The experiments were carried out 24 and 48 h after estradiol, respectively. The LHRH antagonist facilitated the acquisition of CARs in both experimental groups, thus reversing the impairments observed during estrus and metestrus and those induced by estradiol replacement. The antagonist decreased the number of head shakes during estrus, whereas it induced an increase in total motility and rears in ovariectomized control animals. On the other hand, the antagonist increased the number of rears and reversed the decrease in grooming behavior induced by estradiol. The results led to the idea of a role of LHRH in behaviors not apparently related to sex, which could explain the behavioral changes observed across the estrous cycle and those induced by estradiol replacement in ovariectomized rats.