Effects of Photoperiod on Epididymal and Sperm Morphology in a Wild Rodent, the Viscacha (Lagostomus maximus maximus).

The viscacha (Lagostomus maximus maximus) is a seasonal South American wild rodent. The adult males exhibit an annual reproductive cycle with periods of maximum and minimum gonadal activity. Four segments have been identified in the epididymis of this species: initial, caput, corpus, and cauda. The main objective of this work was to relate the seasonal morphological changes observed in the epididymal duct with the data from epididymal sperm during periods of activity and gonadal regression using light and scanning electron microscopy (SEM). Under light and electron microscopy, epididymal corpus and cauda showed marked seasonal variations in structural parameters and in the distribution of different cellular populations of epithelium. Initial and caput segments showed mild morphological variations between the two periods. Changes in epididymal sperm morphology were observed in the periods analyzed and an increased number of abnormal gametes were found during the regression period. During this period, anomalies were found mainly in the head, midpiece, and neck, while in the activity period, defects were found only in the head. Our results confirm that the morphological characteristics of the epididymal segments, as well as sperm morphology, undergo significant changes during the reproductive cycle of Lagostomus.

Allopregnanolone alters the luteinizing hormone, prolactin, and progesterone serum levels interfering with the regression and apoptosis in rat corpus luteum.

Steroids synthesized in the central nervous system are termed "neurosteroids". They are synthesized and metabolized in several brain areas. The objective of this work was to determine if 1 intracerebroventricular allopregnanolone injection in rats can interfere in luteal regression in a close relationship with modifications in LH, progesterone, and prolactin serum concentrations. Allopregnanolone was injected during proestrus morning and the animals were sacrificed on oestrous morning. Ovulation test and histological analysis were performed in the oestrus morning with light and electron microscopy. Serum prolactin, LH, and progesterone levels were measured by radioimmunoassay. The allopregnanolone injection significantly decreased luteinizing hormone serum level and the number of oocytes on oestrus. Progesterone and prolactin serum levels were increased after this injection. The inhibition of apoptotic figures due to allopregnanolone administration was detected in the already formed corpora lutea belonging to the previous ovary cycle and it was significantly lower than in vehicle group (control). When the GABA(A) antagonist (bicuculline) was administered alone or previously to allopregnanolone, no effect on the ovulation rate was observed. No changes in the apoptotic cell numbers were observed with respect to those of vehicle group. These results show that the effect of centrally injected allopreganolone over reproductive function could be due to a centrally originated LH mediated effect over ovarian function that affects luteal regression, through the inhibition of apoptosis and stimulation of progesterone and prolactin release.

Involvement of the mesenteric ganglia on androstenedione, noradrenaline and nitrite release using a testis ex vivo system.

The autonomic nerve fibres converge to the testis along two major pathways, the superior spermatic nerve (SSN) and the inferior spermatic nerve (ISN). The object of this work was to evaluate whether the addition of noradrenaline (NA) in the ganglionic compartment of two ex vivo systems: superior mesenteric ganglion (SMG)-SSN-testis, inferior mesenteric ganglion (IMG)-ISN-testis modulate androstenedione (A2), NA and nitrite release and to determine whether there are secretory differences between the right and the left testis. Each gonad with its respective ganglion was transferred into a cuvette with two compartments and incubated in a Dubnoff metabolic shaker. The testis incubation liquids were collected and analysed for NA by HPLC, A2 by RIA and nitrites by the Griess method. When NA is added to the IMG, A2 and NA release diminishes and nitrite increases in the left testis, while in the right gonad, A2 and NA increase and nitrite decreases. When NA was administered to the SMG, A2 and NA increase and nitrite diminishes in the left gonad, but they show opposite fluctuations in the right testis. These ex vivo systems appear to be excellent models for studying the sympathetic ganglionic control of the testis though A2, NA and nitrite release from the male gonad. It is evident that a better knowledge about the role of catecholamines and nitric oxide in the testis physiology may facilitate the understanding of some reproductive diseases.

The actin filament network associated to Sertoli cell ectoplasmic specializations

Junctional devices in Sertoli cells conform the blood-testis barrier and play a key role in maturation and differentiation of germ cells. The spacial distribution of ectoplasmic specializations of Sertoli cells was studied by beta-actin immunolabelling, using laser confocal and transmission electron microscopy. For confocal microscopy, beta-actin immunolabelling of ectoplasmic specializations was studied over the background of either prosaposin or glutaredoxin immunolabelling of the Sertoli cytoplasm. Labelling was found near the basal lamina, surrounding early spermatocytes (presumably in leptotene-zygotene) or at one of two levels in the seminiferous epithelium: (1) around deep infoldings of the Sertoli cell cytoplasm, in tubular stages before spermiation, and (2) in the superficial part of the seminiferous epithelium, in tubular stages after or during spermiation. For transmission electron microscopy, beta-actin immunolabelling of ectoplasmic specializations was also used. Ectoplasmic specializations were found at two different levels of the seminiferous epithelium. We also used freeze fracture to analyze the characteristics of tubulo-bulbar complexes, a known component of apical ectoplasmic specializations. Also, these different approaches allowed us to study the complex arrangement of the actin cytoskeleton of Sertoli cells branches, which surround germ cells in different stages of the spermatogenic cycle. Our results show a consistent labelling for beta-actin before, during and after the release of spermatozoa in the tubular lumen (spermiation) suggesting a significant role of the actin network in spermatic cell differentiation. In conclusion, significant interrelations among the beta-actin network, the junctional complexes of the blood-testis barrier and the ectoplasmic specializations were detected at different stages of the seminiferous cycle

The actin filament network associated to Sertoli cell ectoplasmic specializations

Junctional devices in Sertoli cells conform the blood-testis barrier and play a key role in maturation and differentiation of germ cells. The spacial distribution of ectoplasmic specializations of Sertoli cells was studied by beta-actin immunolabelling, using laser confocal and transmission electron microscopy. For confocal microscopy, beta-actin immunolabelling of ectoplasmic specializations was studied over the background of either prosaposin or glutaredoxin immunolabelling of the Sertoli cytoplasm. Labelling was found near the basal lamina, surrounding early spermatocytes (presumably in leptotene-zygotene) or at one of two levels in the seminiferous epithelium: (1) around deep infoldings of the Sertoli cell cytoplasm, in tubular stages before spermiation, and (2) in the superficial part of the seminiferous epithelium, in tubular stages after or during spermiation. For transmission electron microscopy, beta-actin immunolabelling of ectoplasmic specializations was also used. Ectoplasmic specializations were found at two different levels of the seminiferous epithelium. We also used freeze fracture to analyze the characteristics of tubulo-bulbar complexes, a known component of apical ectoplasmic specializations. Also, these different approaches allowed us to study the complex arrangement of the actin cytoskeleton of Sertoli cells branches, which surround germ cells in different stages of the spermatogenic cycle. Our results show a consistent labelling for beta-actin before, during and after the release of spermatozoa in the tubular lumen (spermiation) suggesting a significant role of the actin network in spermatic cell differentiation. In conclusion, significant interrelations among the beta-actin network, the junctional complexes of the blood-testis barrier and the ectoplasmic specializations were detected at different stages of the seminiferous cycle

The actin filament network associated to Sertoli cell ectoplasmic specializations

Junctional devices in Sertoli cells conform the blood-testis barrier and play a key role in maturation and differentiation of germ cells. The spacial distribution of ectoplasmic specializations of Sertoli cells was studied by beta-actin immunolabelling, using laser confocal and transmission electron microscopy. For confocal microscopy, beta-actin immunolabelling of ectoplasmic specializations was studied over the background of either prosaposin or glutaredoxin immunolabelling of the Sertoli cytoplasm. Labelling was found near the basal lamina, surrounding early spermatocytes (presumably in leptotene-zygotene) or at one of two levels in the seminiferous epithelium: (1) around deep infoldings of the Sertoli cell cytoplasm, in tubular stages before spermiation, and (2) in the superficial part of the seminiferous epithelium, in tubular stages after or during spermiation. For transmission electron microscopy, beta-actin immunolabelling of ectoplasmic specializations was also used. Ectoplasmic specializations were found at two different levels of the seminiferous epithelium. We also used freeze fracture to analyze the characteristics of tubulo-bulbar complexes, a known component of apical ectoplasmic specializations. Also, these different approaches allowed us to study the complex arrangement of the actin cytoskeleton of Sertoli cells branches, which surround germ cells in different stages of the spermatogenic cycle. Our results show a consistent labelling for beta-actin before, during and after the release of spermatozoa in the tubular lumen (spermiation) suggesting a significant role of the actin network in spermatic cell differentiation. In conclusion, significant interrelations among the beta-actin network, the junctional complexes of the blood-testis barrier and the ectoplasmic specializations were detected at different stages of the seminiferous cycle.

Effects of prenatal exposure to a mild chronic variable stress on body weight, preweaning mortality and rat behavior.

Early stimulation has been shown to produce long-lasting effects in many species. Prenatal exposure to some strong stressors may affect development of the nervous system leading to behavioral impairment in adult life. The purpose of the present work was to study the postnatal harmful effects of exposure to variable mild stresses in rats during pregnancy. Female Holtzman rats were submitted daily to one session of a chronic variable stress (CVS) during pregnancy (prenatal stress; PS group). Control pregnant rats (C group) were undisturbed. The pups of PS and C dams were weighed and separated into two groups 48 h after delivery. One group was maintained with their own dams (PS group, N = 70; C group, N = 36) while the other PS pups were cross-fostered with C dams (PSF group, N = 47) and the other C pups were cross-fostered with PS dams (CF group, N = 58). Pups were undisturbed until weaning (postnatal day 28). The male offspring underwent motor activity tests (day 28), enriched environment tests (day 37) and social interaction tests (day 42) in an animal activity monitor. Body weight was recorded on days 2, 28 and 60. The PS pups showed lower birth weight than C pups (Duncan's test, P<0.05). The PS pups suckling with their stressed mothers displayed greater preweaning mortality (C: 23%, PS: 60%; chi2 test, P<0.05) and lower body weight than controls at days 28 and 60 (Duncan's test, P<0.05 and P<0.01, respectively). The PS, PSF and CF groups showed lower motor activity scores than controls when tested at day 28 (Duncan's test, P<0.01 for PS group and P<0.05 for CF and PSF groups). In the enriched environment test performed on day 37, between-group differences in total motor activity were not detected; however, the PS, CF and PSF groups displayed less exploration time than controls (Duncan's test, P<0.05). Only the PS group showed impaired motor activity and impaired social behavior at day 42 (Duncan's test, P<0.05). In fact, CVS treatment during gestation plus suckling with a previously stressed mother caused long-lasting physical and behavioral changes in rats. Cross-fostering PS-exposed pups to a dam which was not submitted to stress counteracted most of the harmful effects of the treatment. It is probable that prenatal stress plus suckling from a previously stressed mother can induce long-lasting changes in the neurotransmitter systems involved in emotional regulation. Further experiments using neurochemical and pharmacological approaches would be interesting in this model.

Effects of prenatal exposure to a mild chronic variable stress on body weight, preweaning mortality and rat behavior

Early stimulation has been shown to produce long-lasting effects in many species. Prenatal exposure to some strong stressors may affect development of the nervous system leading to behavioral impairment in adult life. The purpose of the present work was to study the postnatal harmful effects of exposure to variable mild stresses in rats during pregnancy. Female Holtzman rats were submitted daily to one session of a chronic variable stress (CVS) during pregnancy (prenatal stress; PS group). Control pregnant rats (C group) were undisturbed. The pups of PS and C dams were weighed and separated into two groups 48 h after delivery. One group was maintained with their own dams (PS group, N = 70; C group, N = 36) while the other PS pups were cross-fostered with C dams (PSF group, N = 47) and the other C pups were cross-fostered with PS dams (CF group, N = 58). Pups were undisturbed until weaning (postnatal day 28). The male offspring underwent motor activity tests (day 28), enriched environment tests (day 37) and social interaction tests (day 42) in an animal activity monitor. Body weight was recorded on days 2, 28 and 60. The PS pups showed lower birth weight than C pups (Duncan's test, 0.05). The PS pups suckling with their stressed mothers displayed greater preweaning mortality (C: 23 percent, PS: 60 percent; 2 test, 0.05) and lower body weight than controls at days 28 and 60 (Duncan's test, 0.05 and 0.01, respectively). The PS, PSF and CF groups showed lower motor activity scores than controls when tested at day 28 (Duncan's test, 0.01 for PS group and ;0.05 for CF and PSF groups). In the enriched environment test performed on day 37, between-group differences in total motor activity were not detected; however, the PS, CF and PSF groups displayed less exploration time than controls (Duncan's test, 0.05). Only the PS group showed impaired motor activity and impaired social behavior at day 42 (Duncan's test, 0.05). In fact, CVS treatment during gestation plus suckling with a previously stressed mother caused long-lasting physical and behavioral changes in rats. Cross-fostering PS-exposed pups to a dam which was not submitted to stress counteracted most of the harmful effects of the treatment. It is probable that prenatal stress plus suckling from a previously stressed mother can

Neonatal chronic stress induces subsensitivity to chronic stress in adult rats: II. Effects on estrous cycle in females.

The purpose of the present report was to determine the effect of exposure of females rats to the unpredictable chronic stress model and two models of predictable chronic stress (cold and handling), from day 2-15 of life, on the estrous cycle alterations caused by the unpredictable chronic stress in adulthood. Adult control and neonatally stressed rats were submitted to estrous cycle analysis for 8 days through microscopic observations of vaginal smears. They were then exposed to chronic aleatory stress, and vaginal smears were analyzed daily throughout the stress period (17 days) up to day 5 after completion of the treatment. It was found that this treatment caused constant diestrus in a majority of control females. Such diestrus started at day 5.75 +/- 0.96 of stress administration and was maintained up to day 20.0 +/- 0.49 (i.e., about 3 days after interruption of stress). This effect was prevented by the neonatal aleatory stress and the neonatal cold stress. Neonatal handling only attenuated the estrous cycle alterations; this group showed a period of diestrus no longer than 4 days during the 17-day exposure to stress. The increased resistance of neonatally stressed rats to the estrous cycle effects of chronic aleatory stress in adulthood supports the speculation that neonatal manipulation can increase resistance of rats to stress-induced reactions throughout life.

Neonatal chronic stress induces subsensitivity to chronic stress in adult rats. I. Effects on forced swim behavior and endocrine responses.

An influence of early stimulation on sensitivity to acute stress in adulthood has been reported. The purpose of the present work was to determine the effect of exposure of male and female rats to three models of chronic stress (unpredictable stress, cold stress and handling) from day 2 to day 15 of life on behavioral and endocrine sensitivity to chronic stresses in adulthood. The chronic stresses applied in adulthood were a model of intermittent cold stress (daily 30-min sessions at -20 degrees C for 15 days) and the Katz's model of unpredictable chronic stress (15 days). Forced swim behavior and serum concentration of the stress-sensitive hormones, corticosterone and prolactin, were chosen to investigate stress sensitivity. It was found that all neonatal treatments stimulated body weight gain, did not cause infant mortality and did not affect forced swim behavior as adult. The repetitive exposure to cold stress in adulthood did not cause major impairment of forced swim behavior and did not affect basal levels of serum corticosterone and prolactin in either control or experimental rats. These findings support the view that repeated stressors can induce behavioral and endocrine adaptation in rats. The neonatal treatments did not affect this characteristic. The exposure of control rats to the unpredictable stress model severely impaired forced swim behavior and increased basal levels of serum corticosterone and prolactin. This observation conforms to the view that standard laboratory rats cannot adapt to unpredictable chronic stress. This has been reported to cause a behavioral depression syndrome comprising forced swim deficit and endocrine alterations.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of lesions of the dorsalis raphe nuclei on the initiation of alcohol preference in rats.

In this report, the effect of lesion of the dorsalis raphe nuclei (DR) by stereotaxic injection of kainic acid on the initiation of voluntary ethanol consumption is described for male rats. After a 30-day recovery period DR- and control-rats were exposed to a 0.2% saccharin sodium--water--5% ethanol free choice test (8 days) for the first time. This three-choice paradigm revealed a positive preference for ethanol (50.5%) vs. saccharin (29.5%) and water (20.0%) in control rats. However, in the group showing histological evidence of DR lesion there was no preference for ethanol (25.7%) whereas total fluid intake/8 days was not affected. These findings suggest a specific effect of the DR lesion on ethanol preference in naive rats. In addition, the within-group analysis of data revealed that such effects were due to an increase in the population of spontaneous non-alcohol-preferring subjects (ethanol preference between 0 and 20%) and to prevention of alcohol-preferring rats (ethanol preference between 80-100%). The depletion of brain serotonin (5-HT) found in the forebrain of the DR-lesioned rats suggests that 5-HT pathways projecting from the DR neurons may be involved in these effects. The fact that forebrain noradrenalin was not affected would rule out involvement of lesions of locus coeruleus-noradrenalin neurons by diffusion of kainic acid. However, the eventual lesion of peptide neurons in the periventricular gray substance surrounding the DR nuclei cannot be discounted.

Excitatory and inhibitory behavioral responses to the pharmacological stimulation of serotonergic function in dorsalis raphe lesioned rats.

Neurotoxin-induced lesions of 5-HT neurons produce supersensitivity of 5-HT1 receptors without affecting 5-HT2 receptor binding in the brain. This model was used in the present work to analyze the role of 5-HT receptor subtypes in the mechanism controlling the excitatory and inhibitory behavioral responses to the pharmacological stimulation of 5-HT systems. Dorsalis raphe (DR) lesions were made by stereotaxic injection of kainic acid. At day 30 after injection DR-and control rats displayed similar baseline behavior in hole board tests. Three days later DR-and control rats received an ip injection of fluoxetine (5 or 10 mg/kg) 30 min before injecting ip 5-HTP(15 or 30 mg/kg). Immediately before and after each ip injection the excitatory response (myoclonic syndrome) was evaluated. DR-and control-group showed similar scores of myoclonus in response to fluoxetine-5-HTP. The inhibitory response was investigated in hole board trials performed 30 min after the second ip injection. The DR lesion potentiated the behavioral depressive effect of fluoxetine-5-HTP. In agreement with data in the literature the DR lesion caused 74.9% loss of forebrain 5-HT and 75% increases of 3H-5HT binding in cortex membranes. Most components of the excitatory response, which remained unchanged in the DR-lesioned rats, might be related to 5-HT2 receptors. The increased inhibitory response to 5-HT stimulation in DR-lesioned rats would be due to the supersensitivity of 5-HT1 receptors.

Excitatory and inhibitory behavioral responses to the pharmacological stimulation of serotonergic function in dorsalis raphe lesioned rats.

Neurotoxin-induced lesions of 5-HT neurons produce supersensitivity of 5-HT1 receptors without affecting 5-HT2 receptor binding in the brain. This model was used in the present work to analyze the role of 5-HT receptor subtypes in the mechanism controlling the excitatory and inhibitory behavioral responses to the pharmacological stimulation of 5-HT systems. Dorsalis raphe (DR) lesions were made by stereotaxic injection of kainic acid. At day 30 after injection DR-and control rats displayed similar baseline behavior in hole board tests. Three days later DR-and control rats received an ip injection of fluoxetine (5 or 10 mg/kg) 30 min before injecting ip 5-HTP(15 or 30 mg/kg). Immediately before and after each ip injection the excitatory response (myoclonic syndrome) was evaluated. DR-and control-group showed similar scores of myoclonus in response to fluoxetine-5-HTP. The inhibitory response was investigated in hole board trials performed 30 min after the second ip injection. The DR lesion potentiated the behavioral depressive effect of fluoxetine-5-HTP. In agreement with data in the literature the DR lesion caused 74.9

loss of forebrain 5-HT and 75

increases of 3H-5HT binding in cortex membranes. Most components of the excitatory response, which remained unchanged in the DR-lesioned rats, might be related to 5-HT2 receptors. The increased inhibitory response to 5-HT stimulation in DR-lesioned rats would be due to the supersensitivity of 5-HT1 receptors.

Effect of the chronic ingestion of chlorimipramine and desipramine on the hole board response to acute stresses in male rats.

The effect of the chronic ingestion of chlorimipramine (CI) or desipramine (DS) on the alterations of hole board behavior caused by a model stress (2 IP injections of physiological saline) and by a short restraint stress (5 min) is analyzed in this study. The experimental groups ingested about 3 mg/kg/24 hr CI or DS for 15 days. Then some experimental and control rats were assigned to control of drug effects on baseline activity. The remaining rats were submitted to saline stress (Experiment I) or restraint stress (Experiment II). The baseline scores of hole board locomotion, head dipping, grooming and defecation were not affected by DS treatment but locomotion slightly increased in the CI treated group. Saline stress impaired significantly head dipping and caused excessive grooming in control rats. The CI treatment induced almost full protection against these behavioral effects of saline stress but DS treatment was ineffective. Restraint stress was found to cause a pronounced inhibition of head dipping as well as a great increase of the scores of grooming in the control group. The CI treatment clearly attenuated these effects of restraint but DS treatment was not effective. The results suggest that male rats treated chronically with CI tolerated both acute stresses better than untreated rats, and that a similar treatment with DS did not provide protection against the effect of such stresses on hole board responding. Inasmuch as CI and DS have different relative potency at noradrenergic and serotonergic systems, it is speculated that this might be in part responsible for their differences as stress protectors.

Behavioral responses of high and low active male rats to the chronic ingestion of desipramine.

Male rats arbitrarily selected for high and low motor activity (HA and LA-rats) were submitted to the chronic ingestion (30 days) of desipramine (DSP) in doses of about 1.5, 3 and 6 mg/kg/24 hr. Their motor activity was assessed in an animal activity monitor providing a measure of total horizontal movements and vertical movements and in a hole-board providing a measure of locomotion, head-dipping and grooming. There were significant differences between HA and LA-rats in their behavioral response to DSP treatment. At the doses used DSP did not affect horizontal and vertical movements and hole-board locomotion or exploration in HA-rats (Experiment 1). In LA-rats, however (Experiment 2), these motor activities were significantly stimulated by DSP. Such effect was dose dependent; 1.5 mg/kg/24 hr was ineffective while 6 mg/kg/24 hr produced a clear cut reversion of hypoactivity. It is speculated that DSP treatment increased resistance of LA-rats to the mild stress caused by testing.

Amniotic fluid thyrotropin (TSH) following maternal administration of thyrotropin releasing hormone.

Cord blood and amniotic fluid thyrotropin (TSH), T4, T3, and rT3 concentrations were measured in 49 women who received 400 micrograms thyrotropin releasing hormone (TRH) iv during labor and in 16 control women who received saline. Cord blood serum TSH concentrations were elevated for as long as 4 hours after TRH administration and peak values (38.0 +/- 4.2 microU/ml) were observed from 61-120 minutes after TSH as compared to control values of 5.0 +/- 0.3 microU/ml. The elevations in fetal TSH concentration stimulated the fetal thyroid, resulting in a progressive increase in cord blood T4 and T3 but not rT3 concentrations. These TRH induced elevations in fetal cord blood TSH concentrations were not accompanied by increases in unconcentrated and 4 fold concentrated amniotic fluid TSH concentrations which were almost always below 0.6 microU/ml, the limit of assay sensitivity. Unconcentrated amniotic fluid T4 concentrations were barely detectable and no variation was observed between the TRH treated and saline treated mothers; amniotic fluid T3 was not detectable in any of the groups; and amniotic fluid rT3 concentrations ranged between 46.4 and 55.6 ng/dl and did not differ between groups. These findings suggest that term amniotic fluid TSH values do not reflect transient but marked elevations in fetal serum TSH concentrations and that amniotic fluid TSH determination is probably not useful in the detection of primary fetal hypothyroidism. It is possible, but unlikely, that long-term and even greater elevations in fetal serum TSH concentrations would result in increased amniotic fluid TSH concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of serotonergic and catecholaminergic antagonists on mild-stress-induced excessive grooming in the rat.

Excessive grooming was induced in male rats by two ip injections of physiological saline. This mild stressful procedure did not modify open-field locomotion in 5-min trials. Methysergide (15 mg/kg) and pizotifene (5 mg/kg), serotonergic blockers, selectively prevented the grooming response to saline without affecting locomotion. Haloperidol (.4 mg/kg) also prevented the excessive grooming. However, this dopaminergic blocker impaired locomotion. The alpha- or beta-adrenoceptor antagonists phentolamine (20 mg/kg) and l-propranolol (20 mg/kg) did not prevent the excessive grooming in response to saline and did not affect locomotion. The results suggest that some serotonergic pathways in the brain are involved in the grooming response to a mild stress and support previous findings on the role of dopaminergic systems on this activity.

Effects of the chronic ingestion of therapeutic doses of chlorimipramine on the behavioral action of agonists and antagonists of serotonin in male rats.

Locomotor activity and hole-board exploration (frequency and time spent head-dipping) were impaired in male rats by injecting IP the 5-HT agonists, fluoxetine and 5-HTP. This treatment produced also myoclonus and increased the time spent resting during trials. The chronic ingestion of chlorimipramine (CIM) or the injection of the 5-HT receptor blocker, methysergide (15 mg/kg) prevented the action of the 5-HT agonists on locomotion and resting and blocked the appearance of myoclonus. Both CIM and methysergide prevented to a minor degree the fluoxetine-5-HTP-induced decrease of exploration. The chronic ingestion of CIM clearly potentiated the effects of methysergide on hole-board exploration. Results suggest that the chronic treatment with therapeutic doses of CIM reduces the functional activity of some 5-HT systems in the brain of the rat, probably by blockade of post-synaptic 5-HT receptors. This does not preclude, however, that CIM may also alter some NA systems.