Nature and nurture of sexual partner preference: Teachings from prenatal administration of acetaminophen in male rats.

The organizational-activational hypothesis indicates that activation of adult sexual behavior in males depends on organization of the masculine brain during the perinatal sensitive period. In the medial preoptic area such masculinization depends on a neuroendocrine cascade that includes exposure to testosterone, aromatization to estradiol, activation of estrogen receptors, synthesis of cyclooxygenase (COX), increase of prostaglandins, release of glutamate, and activation of AMPA receptors that result in the formation of more dendritic spines. Thus, in the present study we assessed the sexual partner preference (SPP) of adult male rats prenatally treated with acetaminophen (APAP), an analgesic/antipyretic drug that inhibits COX-2 and is commonly used and prescribed during pregnancy. Female rats received either saline (2 ml/kg s.c.) or APAP (50 mg/kg s.c.) every 12 h, during days 16-20 of pregnancy. At postnatal day PD60 half of the male offspring were exposed to sexual experience with receptive females during 5 trials, and the other half remained sexually naïve. At PD90 all them were tested for SPP with one sexually receptive female and one stud male. The results indicated that only APAP-naïve males failed to display SPP. However, APAP-experienced males displayed SPP for females. We discuss the effects of prenatal APAP in the disruption of unconditioned responses towards females (nature mechanisms), and the effects of sexual experience (nurture mechanisms) in the development of conditioned heterosexual preference.

Prepuberal stress and obesity: effects on serum corticosterone, prolactin, testosterone and precancerous prostate lesions in adult rats.

Stress during puberty and obesity can represent conditions that facilitate the long-term development of diseases, especially for stress-related disorders that depend on neuroendocrine and immune responses. The prostate is prone to diseases that result from neuroendocrine or immune challenges, such as cancer. AIM: In the present study, we assessed the long-term effects of an acute pubertal stressor (immune-challenge) or obesity on the development of precancerous lesions in rats. MATERIALS AND METHODS: Pubertal male rats received a single injection of lipopolysaccharide (LPS) or saline during puberty (5 weeks of age). In adulthood (8 weeks old), subgroups of males were fed with hypercaloric liquid diet to induce obesity. This resulted in a total of six subgroups: (1) intact-non obese, (2) intact-obese, (3) saline-non obese, (4) saline-obese, (5) LPS-non obese, and (6) LPS-obese. At 16 weeks of age the rats were sacrified for prostate histology (hematoxylin and eosin stain) and hormone analysis (testosterone, corticosterone and prolactin). RESULTS: As compared to intact-non obese rats, males treated with LPS and those with obesity expressed histological alterations in both the dorsolateral and ventral portions of the prostate. Only prolactin was altered in LPS-treated males, whereas corticosterone was altered in LPS-obese rats. CONCLUSIONS: These results indicate that puberal exposure to an immune challenge or obesity facilitate the development of prostatic lesions in adult male rats. We discuss the role of hormones in the development of precancerous lesions.

Somatic innervation contributes to the release of bulbourethral gland secretion in male rats.

BACKGROUND: In male rats, the bulbourethral glands (Bu-Gs) are the unique accessory sexual glands surrounded by striated musculature. However, until now the role of this musculature was unknown. OBJECTIVES: (i) To characterize the Bu-Gs striated muscular layer in male rats and determine its innervation and response to genital stimulation. (ii) To reveal the role of the Bu-Gs striated musculature in the release of glandular secretion. (iii) To elucidate the effect of bilateral ablation of the Bu-Gs on copulatory behavior and seminal fluid characteristics. MATERIALS AND METHODS: Adult Wistar male rats were allocated in three experiments: in Experiment 1, the Bu-Gs striated musculature, innervation and reflex activity were determined by gross anatomy and histological and electrophysiological techniques; electromyographic activity of the Bu-Gs striated musculature was evoked with genital stimulation. In Experiment 2, Bu-Gs were analyzed after copulatory behavior of intact or animals with unilateral transected motor branch of the sacral plexus (MBSP). In Experiment 3, copulatory behavior and spermatobioscopy of males with bilateral ablation of the Bu-Gs or sham surgery were analyzed. RESULTS: The Bu-Gs striated fibers discharged in response to mechanostimulation of the prepuce, glans, and penile-urethra. Innervation of the Bu-Gs striated musculature originated from the MBSP; this nerve also innervates striated penile muscles. Unilateral transection of the MBSP significantly decreased the secretion from the ipsilateral Bu-G to the nerve transection. Bilateral ablation of Bu-Gs did not affect seminal plug formation but decreased semen viscosity. DISCUSSION AND CONCLUSION: The Bu-Gs striated musculature contributes to expel glandular secretion during sexual intercourse. The somatic control of Bu-Gs secretion is additional to the reported autonomic innervation supplied by the cavernosus nerve, which may underlie the synthesis of secretion as well as contraction of Bu-Gs smooth muscle.

Evaluación temporal del efecto del status epilepticus inducido en la rata en desarrollo en la concentración cerebelar de ácido gama-aminobutírico y glutamato / Time course of the effect of status epilepticus induced in the developing rat on gama-amino butyric acid and glutamate cerebellar concentration

INTRODUCCIÓN: El status epilepticus (SE) es un tipo de actividad epiléptica que causa atrofia cerebelar y pérdida de células de Purkinje en humanos y en animales de experimentación. El cerebelo es una región con alto contenido de ácido gama-aminobutírico (GABA) y glutamato, y algunos estudios refieren cambios en su concentración después de las convulsiones. Sin embargo, hasta la fecha no existen estudios que hayan analizado su efecto en diferentes regiones cerebelares en ratas en desarrollo. El objetivo del presente estudio fue realizar un curso temporal del efecto del SE inducido en ratas Wistar de 14 días de edad (P14) sobre el contenido tisular de GABA y glutamato en el vermis y los hemisferios cerebelares. MÉTODOS: El SE se indujo con el modelo de litio-pilocarpina; las ratas control se inyectaron con salina. Seis h, 24 h o 30 días después del inicio del SE o de la aplicación de solución salina, las ratas se anestesiaron y decapitaron, se extrajo su cerebelo y se separaron el vermis y los hemisferios. Las ratas de ambos grupos se anestesiaron y decapitaron, se extrajo su cerebelo y se separaron el vermis y los hemisferios. Ambas regiones se homogeneizaron (ácido perclórico 0,1 M conteniendo metabisulfito de sodio 4 mM) y centrifugaron, y el sobrenadante se empleó para cuantificar la concentración tisular de GABA y glutamato por cromatografía de líquidos de alta resolución acoplada a un detector fluorométrico. RESULTADOS: El SE no modificó la concentración de GABA y glutamato a los diferentes tiempos de análisis ni en el vermis ni en los hemisferios cerebelares. CONCLUSIONES: El cerebelo en desarrollo es resistente a los cambios neuroquímicos a corto y largo plazo producidos por el SE

INTRODUCTION: Status epilepticus (SE) is an epileptic condition that can cause cerebellar atrophy and loss of Purkinje cells in both humans and research animals. Cerebellum is a region rich in γ-aminobutyric acid (GABA) and glutamate, and some studies have shown that their concentrations may be altered after convulsions. However, there are no studies showing the effect of seizures on different cerebellar regions in developing rats. Time course of the effect of status epilepticus induced in the developing rat on γ-amino butyric acid and glutamate cerebellar concentration. METHODS: SE was induced using the lithium-pilocarpine model; control rats were injected with saline solution. At 6h, 24h, and 1 month after SE o saline injection, rats were anaesthetised with pentobarbital and decapitated, and cerebella were extracted. The vermis and hemispheres were dissected and homogenised in 0.1M perchloric acid containing 4mM sodium bisulfite. Homogenates were centrifuged and supernatant was used to quantify GABA, and glutamate tissue concentrations by HPLC coupled with fluorometric detection. RESULTS: SE did not alter GABA and glutamate tissue concentration in the cerebellar vermis and hemispheres. CONCLUSION: The developing rat cerebellum is resistant to both short- and long-term neurochemical changes induced by SE

Time course of the effect of status epilepticus induced in the developing rat on γ-amino butyric acid and glutamate cerebellar concentration. / Evaluación temporal del efecto del status epilepticus inducido en la rata en desarrollo en la concentración cerebelar de ácido γ-aminobutírico y glutamato.

INTRODUCTION: Status epilepticus (SE) is an epileptic condition that can cause cerebellar atrophy and loss of Purkinje cells in both humans and research animals. Cerebellum is a region rich in γ-aminobutyric acid (GABA) and glutamate, and some studies have shown that their concentrations may be altered after convulsions. However, there are no studies showing the effect of seizures on different cerebellar regions in developing rats. Time course of the effect of status epilepticus induced in the developing rat on γ-amino butyric acid and glutamate cerebellar concentration. METHODS: SE was induced using the lithium-pilocarpine model; control rats were injected with saline solution. At 6h, 24h, and 1 month after SE o saline injection, rats were anaesthetised with pentobarbital and decapitated, and cerebella were extracted. The vermis and hemispheres were dissected and homogenised in 0.1M perchloric acid containing 4mM sodium bisulfite. Homogenates were centrifuged and supernatant was used to quantify GABA, and glutamate tissue concentrations by HPLC coupled with fluorometric detection. RESULTS: SE did not alter GABA and glutamate tissue concentration in the cerebellar vermis and hemispheres. CONCLUSION: The developing rat cerebellum is resistant to both short- and long-term neurochemical changes induced by SE.

Olfactory conditioned same-sex partner preference in female rats: Role of ovarian hormones.

The dopamine D2-type receptor agonist quinpirole (QNP) facilitates the development of conditioned same-sex partner preference in males during cohabitation, but not in ovariectomized (OVX) females, primed with estradiol benzoate (EB) and progesterone (P). Herein we tested the effects of QNP on OVX, EB-only primed females. Females received a systemic injection (every four days) of either saline (Saline-conditioned) or QNP (QNP-conditioned) and then cohabited for 24h with lemon-scented stimulus females (CS+), during three trials. In test 1 (female-female) preference was QNP-free, and females chose between the CS+ female and a novel female. In test 2 (male-female) they chose between the CS+ female and a sexually experienced male. In test 1 Saline-conditioned females displayed more hops & darts towards the novel female, but QNP-conditioned females displayed more sexual solicitations towards the CS+ female. In test 2 Saline-conditioned females displayed a clear preference for the male, whereas QNP-conditioned females displayed what we considered a bisexual preference. We discuss the effect of dopamine and ovarian hormones on the development of olfactory conditioned same-sex preference in females.

Efecto de la lesión electrolítica del estriado dorsomedial sobre la conducta sexual y actividad locomotora de la rata / Effect of electrolytic lesion of the dorsomedial striatum on sexual behaviour and locomotor activity in rats

Introducción: Las áreas motoras corticales no solo son influenciadas por aferencias sensitivas periféricas y áreas de asociación prefrontales, sino también por los ganglios basales, específicamente el estriado. El estriado dorsomedial (EDM) y el estriado dorsolateral están involucrados en el aprendizaje espacial y el aprendizaje estímulo-respuesta; sin embargo, cada una de estas zonas pudiera mediar distintos componentes del aprendizaje. El propósito del estudio es determinar el efecto de la lesión electrolítica del EDM sobre el aprendizaje y ejecución de la conducta locomotora y sexual en ratas macho. Método: Una vez que los sujetos aprendieron a ejecutar las pruebas motoras de equilibrio, laberinto, rampa de ascenso y la conducta sexual, se realizó la lesión electrolítica del EDM. Cinco días después se realizaron las pruebas en 2 ocasiones más y se compararon las latencias de ejecución de cada prueba. Resultados: Después de la lesión, los valores promedio de latencia, incrementaron durante la ejecución de las pruebas de laberinto y equilibrio. Sin embargo, los valores promedio en la prueba rampa y conducta sexual, no aportaron efectos contrastantes entre los grupos. Conclusiones: La lesión electrolítica del EDM modifica la ejecución de la actividad locomotora (prueba de laberinto y equilibrio), pero no la ejecución de la conducta sexual (AU)

Introduction: Cortical motor areas are influenced not only by peripheral sensory afferents and prefrontal association areas, but also by the basal ganglia, specifically the striatum. The dorsomedial striatum (DMS) and dorsolateral striatum are involved in both spatial and stimulus-response learning; however, each of these areas may mediate different components of learning. The aim of the study is to determine the effect of electrolytic lesion to the DMS on the learning and performance of sexual behaviour and locomotor activity in male rats. Method: Once the subjects had learned to perform motor tests of balance, maze navigation, ramp ascent, and sexual behaviour, they underwent electrolytic lesion to the DMS. Five days later, the tests were repeated on 2 occasions and researchers compared performance latencies for each test. Results: Average latency values for performance on the maze and balance tests were higher after the lesion. However, the average values for the ramp test and for sexual behaviour did not differ between groups. Conclusions: Electrolytic lesion of the DMS modifies the performance of locomotor activity (maze test and balance), but not of sexual behavior (AU)

Effect of electrolytic lesion of the dorsomedial striatum on sexual behaviour and locomotor activity in rats. / Efecto de la lesión electrolítica del estriado dorsomedial sobre la conducta sexual y actividad locomotora de la rata.

INTRODUCTION: Cortical motor areas are influenced not only by peripheral sensory afferents and prefrontal association areas, but also by the basal ganglia, specifically the striatum. The dorsomedial striatum (DMS) and dorsolateral striatum are involved in both spatial and stimulus-response learning; however, each of these areas may mediate different components of learning. The aim of the study is to determine the effect of electrolytic lesion to the DMS on the learning and performance of sexual behaviour and locomotor activity in male rats. METHOD: Once the subjects had learned to perform motor tests of balance, maze navigation, ramp ascent, and sexual behaviour, they underwent electrolytic lesion to the DMS. Five days later, the tests were repeated on 2 occasions and researchers compared performance latencies for each test. RESULTS: Average latency values for performance on the maze and balance tests were higher after the lesion. However, the average values for the ramp test and for sexual behaviour did not differ between groups. CONCLUSIONS: Electrolytic lesion of the DMS modifies the performance of locomotor activity (maze test and balance), but not of sexual behaviour.

Effect of copulation on potentially precancerous prostate lesions, serum testosterone and prolactin levels in rats.

UNLABELLED: The prostate is an exocrine reproductive gland that participates in ejaculation and it is prone to diseases, including cancer. AIM: In the pre-sent study, we assessed the long-term effects of copulation on the development of precancerous lesions in rats, and compared them with testosterone-induced prostatic lesions. MATERIALS AND METHODS: One group of Wistar males was given 10 copulatory sessions to one ejaculation with ovariectomized, hormone-primed females. Sessions occurred twice per week for a total of ten trials. A second group was exposed to females during the same trials, but physical contact was prevented. In addition, each group received a subcutaneous implant in the back either filled with testosterone propionate (T, 100 mg/kg) or empty. This resulted in four subgroups: 1) Control + No sex, 2) Control + Sex, 3) T + No sex and 4) T + Sex. Two days after the 10(th) trial all the males were sacrificed for prostate histo-logy (H&E) and hormone analysis (testosterone and prolactin). RESULTS: Males from the group Control + No sex expressed normal histo-logy. However, those in the groups Control + Sex and T + No sex expressed metaplasia and dysplasia in both the dorsolateral and ventral portions of the prostate, respectively. Interestingly, males from the group T + Sex expressed dysplasia in the dorsolateral prostate only, but not in the ventral prostate. CONCLUSIONS: These results indicate that constant copulation may facilitate the development of prostatic lesions in males with normal levels of testosterone. However, copulation induces less lesions in the ventral prostate of males treated with testosterone.

The formation of the smallest fullerene-like carbon cages on metal surfaces.

The nucleation and growth of carbon on catalytically active metal surfaces is one of the most important techniques to produce nanomaterials such as graphene or nanotubes. Here it is shown by in situ electron microscopy that fullerene-like spherical clusters with diameters down to 0.4 nm and thus much smaller than C60 grow in a polymerized state on Co, Fe, or Ru surfaces. The cages appear on the surface of metallic islands in contact with graphene under heating to at least 650 °C and successively cooling to less than 500 °C. The formation of the small cages is explained by the segregation of carbon on a supersaturated metal, driven by kinetics. First principles energy calculations show that the clusters polymerize and can be attached to defects in graphene. Under compression, the polymerized cages appear in a crystalline structure.

Activación del cerebelo por estimulación olfativa en ratas macho sexualmente inexpertas / Activation of the cerebellum by olfactory stimulation in sexually naive male rats

Introducción: El cerebelo es una estructura que se ha vinculado con múltiples funciones, tales como control motor, cognición, memoria y procesamiento emocional. En cuanto a su relación con los sistemas sensoriales no está claro el papel que desempeña en relación con el sentido del olfato. Suponemos que las ratas macho sexualmente inexpertas presentarán un incremento en la actividad neuronal del vermis cerebelar tras ser estimuladas con olor de hembra receptiva y almendra. Métodos: Comparamos la actividad de la capa granular del vermis cerebelar mediante la inmunorreactividad a Fos tras estimulación olfativa. Esta estimulación se realizó durante 60 min en cámaras cúbicas de acrílico con un doble fondo. Los estímulos fueron aserrín limpio, con esencia de almendra y proveniente de la cama de hembras receptivas. Finalmente los machos fueron anestesiados con pentobarbital sódico intraperitoneal. El tejido cerebelar fue fijado con paraformaldehído para su posterior análisis inmunohistoquímico. Resultados: El número de células inmunorreactivas a Fos en todos los lóbulos del vermis cerebelar de los grupos estimulados con almendra y hembra receptiva fue similar, pero mayor comparado con el grupo de aserrín limpio. Conclusiones: La estimulación olfativa del sistema olfatorio principal (almendra) y accesorio (hembra receptiva) incrementa la producción de proteína Fos en la capa granular de la corteza cerebelar del vermis de ratas macho sexualmente inexpertas

Introduction: The cerebellum has been linked to multiple functions, such as motor control, cognition, memory, and emotional processing. As for its involvement in the sensory systems, the role of the cerebellum in the sense of smell remains unclear. We suggest that sexually naive male rats will present increased neuronal activity in the cerebellar vermis after being stimulated with almond odour or oestrous odour from receptive females. Methods: We compared activity in the cerebellar vermis using Fos immunoreactivity after olfactory stimulation. Stimulation took place during 60 min in a cube-shaped acrylic chamber with a double bottom. Stimuli were clean woodchip bedding, bedding with almond extract, and bedding taken from a cage of receptive females. Male rats were subsequently anaesthetised with intraperitoneal sodium pentobarbital. Cerebellar tissue was fixed with paraformaldehyde for later immunohistochemical analysis. Results: The number of Fos immunoreactive cells in all lobes of the cerebellar vermis was similar between groups stimulated with almond extract and with oestrous odour, and higher than in the clean woodchip group. Conclusions: Stimulation of the main olfactory system (almond) and the accessory system (oestrous odour) increases Fos protein production in the granular layer of the cortex of the cerebellar vermis in naive male rats

Long-term administration of prolactin or testosterone induced similar precancerous prostate lesions in rats.

UNLABELLED: Evidence indicates that prolactin plays a crucial role in the normal function and development of the prostate, but abnormal high levels of the hormone are associated with hyperplasia and cancer of the gland. AIMS: The present study was designed to describe the progressive specific histological abnormalities in the prostate of rats with chronic hyperprolactinemia. MATERIAL AND METHODS: Prolactin was administered during 4; 12 or 24 weeks, and the resulting prostatic alterations were compared with control rats, and also with those treated with testosterone, or the combination of prolactin + testosterone. RESULTS: Rats treated with prolactin, testosterone or prolactin + testosterone expressed precancerous histological abnormalities in the dorsolateral and ventral portions of the prostate as early as in 4 weeks of treatment, but in all cases the malignancy increased after 12 or 24 weeks of treatment. CONCLUSION: Our study confirms that chronic hyperprolactinemia is a cause of prostate precancerous pathologies.

Activation of the cerebellum by olfactory stimulation in sexually naive male rats.

INTRODUCTION: The cerebellum has been linked to multiple functions, such as motor control, cognition, memory, and emotional processing. As for its involvement in the sensory systems, the role of the cerebellum in the sense of smell remains unclear. We suggest that sexually naive male rats will present increased neuronal activity in the cerebellar vermis after being stimulated with almond odour or oestrous odour from receptive females. METHODS: We compared activity in the cerebellar vermis using Fos immunoreactivity after olfactory stimulation. Stimulation took place during 60 min in a cube-shaped acrylic chamber with a double bottom. Stimuli were clean woodchip bedding, bedding with almond extract, and bedding taken from a cage of receptive females. Male rats were subsequently anaesthetised with intraperitoneal sodium pentobarbital. Cerebellar tissue was fixed with paraformaldehyde for later immunohistochemical analysis. RESULTS: The number of Fos immunoreactive cells in all lobes of the cerebellar vermis was similar between groups stimulated with almond extract and with oestrous odour, and higher than in the clean woodchip group. CONCLUSIONS: Stimulation of the main olfactory system (almond) and the accessory system (oestrous odour) increases Fos protein production in the granular layer of the cortex of the cerebellar vermis in naive male rats.

Inducción del temblor mandibular por lesión electrolítica del estriado ventrolateral y por el tratamiento subcrónico con haloperidol en rata macho: un contraste electromiográfico / Induction of mandibular tremor using electrolytic lesion of the ventrolateral striatum or using subchronic haloperidol therapy in male rats: An electromyographic comparison

Introducción: El temblor mandibular (TM) en la rata es inducido farmacológicamente por la manipulación dopaminérgica estriatal y por lesión del estriado ventrolateral (EVL). Este temblor tiene características neuroquímicas, anatómicas y electromiográficas similares al temblor que presentan los pacientes con parkinsonismo. Pero se desconocen las características electromiográficas de los temblores generados por la lesión electrolítica del EVL. Método: En ese estudio, se describió electromiográficamente el temblor mandibular generado por la lesión electrolítica bilateral del EVL y se comparó con el inducido por el tratamiento subcrónico (i.p.) con haloperidol, neuroléptico de selectividad alta como antagonista dopaminérgico del receptor D2. A ratas con lesión en la región ventrolateral del estriado, con un tratamiento subcrónico de haloperidol, y a un grupo control que solo recibió el vehículo, se les registró la actividad electromiografía del músculo temporal en condiciones basales y durante los TM. Resultados: La distribución de frecuencias del TM entre los grupos varió, puesto que las ratas con la lesión en el EVL mostraron TM de mayor amplitud y frecuencia EMG que las ratas tratadas con el haloperidol. La amplitud en condiciones basales difirió en los distintos grupos de ratas. Conclusiones: Se concluye que los TM asociados a la lesión electrolítica del EVL son de mayor amplitud y frecuencia que los generados por haloperidol, esto puede estar relacionado con el tipo de afectación estriatal

Introduction: Tremulous jaw movement (TJMs) in rats can be induced pharmacologically by striatal dopaminergic manipulation or electrolytic lesion of ventrolateral striatum (VLS). This tremor has neurochemical, anatomical and electromyographic (EMG) characteristics similar to those of tremor in Parkinson patients. However, the EMG characteristics of tremors generated by electrolytic lesion to the VLS have not yet been studied. Method: This study used electromyography to describe tremulous jaw movement generated by bilateral electrolytic lesion in the VLS and compare it to tremors induced using subchronic IP treatment with haloperidol, a dopaminergic D2 receptor antagonist. The experimental groups contained rats with a lesion in the ventrolateral striatum and rats on subchronic haloperidol treatment; the control group received only the vehicle. The EMG signal from the temporal muscle was recorded at baseline and during TJMs in all groups. Results: TMJ frequencies were heterogeneous among the groups. Rats with VLS lesion showed higher amplitude and frequency values than the haloperidol-treated rats. Amplitudes at baseline also differed among the groups. Conclusions: We conclude that TMJs associated with electrolytic lesion to the VLS show a higher frequency and amplitude than tremors induced by haloperidol. This may be related to the way striatum neurons are affected

Brain activation by an olfactory stimulus paired with juvenile play in female rats.

We have previously shown that reward experienced during social play at juvenile age can be paired with artificial odors, and later in adulthood facilitate olfactory conditioned partner preferences (PP) in female rats. Herein, we examined the expression of FOS immunoreactivity (FOS-IR) following exposure to the odor paired with juvenile play (CS+). Starting at day P31 females received daily 30-min periods of social play with lemon-scented (paired group) or unscented females (unpaired group). At day P42, they were tested for play-PP with two juvenile males, one bearing the CS+ (lemon) and one bearing a novel odor (almond). Females were ovariectomized, hormone-primed and at day P55 tested for sexual-PP between two adult stud males scented with lemon or almond. In both tests, females from the paired group displayed conditioned PP (play or sexual) toward males bearing the CS+. In the present experiments females were exposed at day P59 to the CS+ during 60 min and their brains processed for FOS-IR. One group of female rats (Play+Sex) underwent play-PP and sexual-PP, whereas a second group of females (Play-only) underwent exclusively play-PP but not sexual-PP. Results showed that in the Play-only experiment exposure to the CS+ induced more FOS-IR in the medial prefrontal cortex, orbitofrontal cortex, dorsal striatum, and ventral tegmental area as compared to females from the unpaired group. In the Play+Sex experiment, more FOS-IR was observed in the piriform cortex, dorsal striatum, lateral septum, nucleus accumbens shell, bed nucleus of the stria terminalis and medial amygdala as compared to females from the unpaired group. Taken together, these results indicate mesocorticolimbic brain areas direct the expectation and/or choice of conditioned partners in female rats. In addition, transferring the meaning of play to sex preference requires different brain areas.

Beyond the basal ganglia: cFOS expression in the cerebellum in response to acute and chronic dopaminergic alterations.

The suggestion of an anatomical and functional relationship between the basal ganglia and cerebellum is recent. Traditionally, these structures were considered as neuronal circuits working separately to organize and control goal-directed movements and cognitive functions. However, several studies in rodents and primates have described an anatomical interaction between cortico-basal and cortico-cerebellar networks. Most importantly, functional changes have been observed in one of these circuits when altering the other one. In this context, we aimed to accomplish an extensive description of cerebellar activation patterns using cFOS expression (cFOS-IR) after acute and chronic manipulation of dopaminergic activity. In the acute study, substantia nigra pars compacta (SNc) activity was stimulated or suppressed by intra cerebral administration of picrotoxin or lidocaine, respectively. In addition, we analyzed cerebellar activity after the induction of a parkinsonism model, the tremulous jaw movements. In this model, tremulous jaw movements were induced in male rats by IP chronic administration of the dopamine antagonist haloperidol (1.5mg/kg). Acute stimulation of SNc by picrotoxin increased cFOS-IR in the vermis and cerebellar hemispheres. However, lidocaine did not produce an effect. After 14days of haloperidol treatment, the vermis and cerebellar hemispheres showed an opposite regulation of cFOS expression. Chronic dopaminergic antagonism lessened cFOS expression in the vermis but up-regulated such expression in the cerebellar hemisphere. Overall, the present data indicate a very close functional relationship between the basal ganglia and the cerebellum and they may allow a better understanding of disorders in which there are dopamine alterations.

Induction of mandibular tremor using electrolytic lesion of the ventrolateral striatum or using subchronic haloperidol therapy in male rats: an electromyographic comparison.

INTRODUCTION: Tremulous jaw movement (TJMs) in rats can be induced pharmacologically by striatal dopaminergic manipulation or electrolytic lesion of ventrolateral striatum (VLS). This tremor has neurochemical, anatomical and electromyographic (EMG) characteristics similar to those of tremor in Parkinson patients. However, the EMG characteristics of tremors generated by electrolytic lesion to the VLS have not yet been studied. METHOD: This study used electromyography to describe tremulous jaw movement generated by bilateral electrolytic lesion in the VLS and compare it to tremors induced using subchronic IP treatment with haloperidol, a dopaminergic D2 receptor antagonist. The experimental groups contained rats with a lesion in the ventrolateral striatum and rats on subchronic haloperidol treatment; the control group received only the vehicle. The EMG signal from the temporal muscle was recorded at baseline and during TJMs in all groups. RESULTS: TMJ frequencies were heterogeneous among the groups. Rats with VLS lesion showed higher amplitude and frequency values than the haloperidol-treated rats. Amplitudes at baseline also differed among the groups. CONCLUSIONS: We conclude that TMJs associated with electrolytic lesion to the VLS show a higher frequency and amplitude than tremors induced by haloperidol. This may be related to the way striatum neurons are affected.

The effects of enriched environment on BDNF expression in the mouse cerebellum depending on the length of exposure.

Environmental enrichment (EE) has been proposed as a factor that improves neuronal connectivity and brain plasticity. The induction of molecular mechanisms that takes place in the cortex, nucleus accumbens and hippocampus resulting from exposure to EE has been attributed partly to the role of neurotrophins as brain-derived neurotrophic factor (BDNF). Recent data directly implicate this neurotrophin in the modulation of plasticity changes in the cerebellum produced by living under environmental enrichment. In the present study, we aimed to assess the effects of different lengths of exposure to EE on cerebellar BDNF expression and western blotting analysis. On the whole, the present data has shown that BDNF increased under EE. However, changes in expression as a result of extending the duration of EE were only seen in Purkinje neurons. In Purkinje neurons, long-term exposure was required in order to fully express this neurotrophin. These data support BDNF as one of the long-term plasticity mechanisms induced by environment, suggesting that cerebellar plasticity can be stimulated as a response to challenges generated by environment. Our findings could have functional implications for various neurodegenerative disorders such as spinocerebellar ataxias, autism, schizophrenia and certain prion encephalopathies, most of them pathologies which have demonstrated to be characterized by alterations in Purkinje neurons and to show a partial recovery by exposure to EE.

Inhibition of endoplasmic reticulum Ca²âº ATPase in preBötzinger complex of neonatal rat does not affect respiratory rhythm generation.

PreBötzinger complex (preBötC) neurons in the brainstem underlie respiratory rhythm generation in vitro. As a result of network interactions, preBötC neurons burst synchronously to produce rhythmic premotor inspiratory activity. Each inspiratory neuron has a characteristic 10-20 mV, 0.3-0.8 s synchronous depolarization known as the inspiratory drive potential or inspiratory envelope, topped by action potentials (APs). Mechanisms involving Ca(2+) fluxes have been proposed to underlie the initiation of the inspiratory drive potential. An important source of intracellular Ca(2+) is the endoplasmic reticulum (ER) in which active Ca(2+) sequestration is mediated by a class of transporters termed sarco/endoplasmic reticulum Ca(2+) ATPases (SERCAs). We aim to test the hypothesis that disruption of Ca(2+) sequestration into the ER affects respiratory rhythm generation. We examined the effect of inhibiting SERCA on respiratory rhythm generation in an in vitro slice preparation. Bath application of the potent SERCA inhibitors thapsigargin or cyclopiazonic acid (CPA) for up to 90 min did not significantly affect the period or amplitude of respiratory-related motor output or integral and duration of inspiratory drive in preBötC neurons. We promoted the depletion of intracellular Ca(2+) stores by a transient bath application of 30 mM K(+) (high K(+)) in the continuous presence of thapsigargin or CPA. After washing out the high K(+), respiratory rhythm period and amplitude returned to baseline values. These results show that after inhibition of SERCA and depletion of intracellular Ca(2+) stores, respiratory rhythm remains substantially the same, suggesting that this source of Ca(2+) does not significantly contribute to rhythm generation in the preBötC in vitro.

Amino acid tissue levels and GABAA receptor binding in the developing rat cerebellum following status epilepticus.

Incidence of status epilepticus (SE) is higher in children than in adults and SE can be induced in developing rats. The cerebellum can be affected after SE; however, consequences of cerebellar amino acid transmission have been poorly studied. The goal of this study was to determine amino acid tissue concentration and GABA(A) receptor binding in the immature rat cerebellum after an episode of SE. Thirteen-day-old (P13) rat pups received intraperitoneal injections of lithium chloride (3 mEq/kg). Twenty hours later, on P14, SE was induced by subcutaneous injection of pilocarpine hydrochloride (60 mg/kg). Control animals were given an equal volume of saline subcutaneously. Animals were killed 24h after SE induction, the cerebellum was quickly removed, and the vermis and hemispheres were rapidly dissected out on ice. Amino acid tissue concentrations in the vermis and hemispheres were evaluated by HPLC and fluorescent detection. GABA(A) receptor binding in the medial vermis was analyzed by in vitro autoradiography. SE increased the tissue levels of the inhibitory amino acids taurine (80%) and alanine (91%), as well as glutamine (168%) in the cerebellar hemisphere; no changes were observed in the vermis. SE did not modify GABA(A) receptor binding in any cerebellar lobule from the vermis. Our data demonstrate that SE produces region-specific changes in amino acid concentrations in the developing cerebellum.