Effects of sodium valproate and carbamazepine on food competition aggression in pigeons.

Valproate and carbamazepine (CAR) have been proposed as adjunct alternatives for the control of aggression in psychiatric patients, although no definite conclusions have been reached. We examined the effects of these drugs on food competition offensive aggression and other behaviors in high- and low-aggression food-restricted pigeons. These were divided into pairs containing previously ranked high-aggression (N = 10 pairs) and low-aggression females (N = 10 pairs). In Experiment 1, a pigeon in each pair of high- and low-aggression subjects was treated daily with an oral dose of sodium valproate (50 mg kg-1 mL saline-1) for 15 days. The other animal received the vehicle. On days 1, 7, and 15, food competition trials (10 min) were performed 60 min after treatment. In Experiment 2, one pigeon in each pair was treated daily with an oral dose of CAR (20 mg kg-1 mL saline-1) for 15 days. Each pair was submitted to a food competition trial on days 1, 7, and 15 of treatment. Valproate (15 days of treatment) selectively decreased the time spent in offensive aggression (control: 102.7 +/- 9.3 vs valproate: 32.7 +/- 9.2 s; P < 0.001, ANOVA-2-TAU) of high-aggression pigeons. This was also the case for 7 and 15 days of CAR treatment (control: 131.5 +/- 8.9 vs CAR: 60.4 +/- 5.3, P < 0.01, and control: 122.7 +/- 7.1 vs CAR: 39.1 +/- 5.2; P < 0.001, ANOVA-2-TAU, respectively). Thus, the two anticonvulsive drugs have a similar effect on food competition aggression in pigeons.

Effects of sodium valproate and carbamazepine on food competition aggression in pigeons

Valproate and carbamazepine (CAR) have been proposed as adjunct alternatives for the control of aggression in psychiatric patients, although no definite conclusions have been reached. We examined the effects of these drugs on food competition offensive aggression and other behaviors in high- and low-aggression food-restricted pigeons. These were divided into pairs containing previously ranked high-aggression (N = 10 pairs) and low-aggression females (N = 10 pairs). In Experiment 1, a pigeon in each pair of high- and low-aggression subjects was treated daily with an oral dose of sodium valproate (50 mg kg-1 mL saline-1) for 15 days. The other animal received the vehicle. On days 1, 7, and 15, food competition trials (10 min) were performed 60 min after treatment. In Experiment 2, one pigeon in each pair was treated daily with an oral dose of CAR (20 mg kg-1 mL saline-1) for 15 days. Each pair was submitted to a food competition trial on days 1, 7, and 15 of treatment. Valproate (15 days of treatment) selectively decreased the time spent in offensive aggression (control: 102.7 ± 9.3 vs valproate: 32.7 ± 9.2 s; P < 0.001, ANOVA-2-TAU) of high-aggression pigeons. This was also the case for 7 and 15 days of CAR treatment (control: 131.5 ± 8.9 vs CAR: 60.4 ± 5.3, P < 0.01, and control: 122.7 ± 7.1 vs CAR: 39.1 ± 5.2; P < 0.001, ANOVA-2-TAU, respectively). Thus, the two anticonvulsive drugs have a similar effect on food competition aggression in pigeons.

Effect of naloxone on food competition aggression in food-restricted high and low aggression pigeons (Columba livia).

We determined the effect of the opiate receptor antagonist naloxone on aggression, emotion, feeder control, and eating behavior in high and low aggression female pigeons maintained at 80% of their normal weight and exposed to food competition interactions. Pigeons were divided into pairs by previously ranked high aggression (total time spent in offensive aggression exceeding 60 s/5 min; N=6 pairs) and low aggression females (time spent in offensive aggression less than 10 s/5 min; N=6 pairs). A pigeon in each pair received an s.c. dose of naloxone (1 mg kg(-1) ml saline(-1)) and the other animal received the vehicle. Trials (10 min) were performed 30 min after the naloxone/vehicle administration. The naloxone group of high aggression pigeons showed lower scores of total time spent in offensive aggression (control: 98.6 +/- 12.0; naloxone: 46.8 +/- 6.6 s; P<0.05) and higher scores of time spent in emotional responses (control: 3.5 +/- 0.6; naloxone: 10.8 +/- 2.4 s; P<0.05) than controls. The other behaviors scored, feeder control and eating behavior, were not affected in this group. The naloxone group of low aggression pigeons, however, showed higher scores of offensive aggression than their controls (5.3 +/- 1.3; naloxone: 28.7 +/- 8.0 s; P<0.05). The present results suggest that opiate receptor mechanisms are implicated in offensive aggression responses in high and low aggression pigeons. However, as reported for brain 5-hydroxytryptamine manipulation and GABA-A-benzodiazepine receptor manipulation, the effect of the opiate receptor antagonist on food competition aggression in pigeons was related to their pretreatment level of aggression.

Effect of naloxone on food competition aggression in food-restricted high and low aggression pigeons (Columba livia)

We determined the effect of the opiate receptor antagonist naloxone on aggression, emotion, feeder control, and eating behavior in high and low aggression female pigeons maintained at 80 percent of their normal weight and exposed to food competition interactions. Pigeons were divided into pairs by previously ranked high aggression (total time spent in offensive aggression exceeding 60 s/5 min; N = 6 pairs) and low aggression females (time spent in offensive aggression less than 10 s/5 min; N = 6 pairs). A pigeon in each pair received an sc dose of naloxone (1 mg kg-1 ml saline-1) and the other animal received the vehicle. Trials (10 min) were performed 30 min after the naloxone/vehicle administration. The naloxone group of high aggression pigeons showed lower scores of total time spent in offensive aggression (control: 98.6 ± 12.0; naloxone: 46.8 ± 6.6 s; P < 0.05) and higher scores of time spent in emotional responses (control: 3.5 ± 0.6; naloxone: 10.8 ± 2.4 s; P < 0.05) than controls. The other behaviors scored, feeder control and eating behavior, were not affected in this group. The naloxone group of low aggression pigeons, however, showed higher scores of offensive aggression than their controls (5.3 ± 1.3; naloxone: 28.7 ± 8.0 s; P < 0.05). The present results suggest that opiate receptor mechanisms are implicated in offensive aggression responses in high and low aggression pigeons. However, as reported for brain 5-hydroxytryptamine manipulation and GABA-A-benzodiazepine receptor manipulation, the effect of the opiate receptor antagonist on food competition aggression in pigeons was related to their pretreatment level of aggression.

Effects of diazepam and flumazenil on food competition behavior in high- and low-aggression pigeons.

The food competition interaction test performed with food-restricted pigeons with previously consolidated dominance is a useful tool for the study of offensive and defensive social aggression. In the present study, we examined the effect of GABA-A-benzodiazepine (BZD) receptor manipulation on aggression, emotion, feeder control, and eating behavior in high- and low-aggression female pigeons maintained at 80% of their normal weight and exposed to food competition interactions. The pigeons were divided into pairs by previously ranked high-aggression females (total time spent in aggression over 60 s/5 min; n=6 pairs) and low-aggression females (time spent in aggression less than 10 s/5 min; n=6 pairs). In Experiment 1, a pigeon in each pair of high- and low-aggression subjects were treated daily with an oral dose of diazepam (DZP, 0.6 mg/kg/0.3 ml) for 8 days. The other animal received the vehicle. On Day 8, food competition trials (10 min) were performed 30 min after treatments. In Experiment 2, pigeons were injected subcutaneously with flumazenil (FZL, 0.1 mg/kg/1 ml) or saline and exposed to a food competition trial 30 min after injections. In Experiment 3, one animal in each pair received DZP for 8 days. The other animal received the vehicle. On Day 8, the DZP-treated subjects were injected subcutaneously with FZL (0.1 mg/ kg/1 ml) 30 min before the oral dose of DZP. Trials were performed 30 min after DZP or vehicle administration. In Experiment 1, it was found that the DZP group of high-aggression pigeons showed lower scores of aggression (P<.05) and emotional responses (P<.05) than controls. The other group-scored behaviors were not affected. The DZP low-aggressions, however, showed scores of aggression eightfold higher than their controls (P<.05) but the other scored behaviors were not changed. In Experiment 2, FZL injection did not induce intrinsic effects on aggression either in the high- or in the low-aggression group. Experiment 3 showed that the emotional and aggressive responses to DZP were neutralized by FZL. This shows that GABA-A-BZD receptor mechanisms are implicated in the DZP responses in high- and low-aggression pigeons.

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

Permanent and transient effects of repeated preweaning stress on social and sexual behaviors of rats.

We have reported that exposure of preweaning male and female rats to a model of unpredictable mild physical stressors (Neo-A) can decrease the behavioral and hormonal responses to acute and chronic stress as adults. In this paper we have analyzed the effect of Neo-A on development of social behaviors, including aggressiveness, social dominance, and sexual behavior in adulthood. The subjects were divided into two groups: Neo-A (daily exposed to unpredictable mild stresses- from day 2 up to day 15 of suckling; n = 30 litters) and controls (C) (undisturbed rats, except for testing, during the same period of life; n = 26 litters). When day 6 pups were submitted to a social clustering test the Neo-A group showed a higher rate of litter-mate clustering than C. The 35 days Neo-A males and Neo-A females submitted to a social behavior test after 24 h of social isolation also showed higher scores of time spent in active social interaction than controls, as well as a higher ratio of animals showing aggressive playing. A second social behavior test performed after 48 h of social isolation at days 75-80 of age revealed that only Neo-A females displayed increased social behavior and aggressive behaviors, whereas controls did not. A water competition test performed at 24 and 48 h after water deprivation showed that Neo-A adult males spent more time in possession of the drinking device and drank more frequently than C. When adult proestrous females were exposed to a sexual behavior test, the Neo-A group showed shorter latency and higher scores of lordosis quotient. These results support the view that exposure to this model of repeated mild stress early in life stimulates the development of social behavior, dominance and sexual behavior.

Effect of the i.c.v. injection of 5,7-di-hydroxytryptamine on the aggressive behavior of dominant and submissive pigeons (Columba livia).

The acute and chronic treatment with 5-HTP was reported to block the aggressive reaction induced by food competition in undernourished dominant pigeons. Such treatment was not effective, however, in submissive pigeons. In this report we describe the effect of the neurotoxine 5, 7-DHT on aggression, defense, emotion, feeder control, and other behaviors in dominant and submissive male pigeons maintained at 80% of their normal weight. These were ranked through daily food competition trials. To obtain the prelesion scores dominant (n = 15) and submissive pigeons (n = 16) were submitted to a daily trial against a different intermediate subject (six trials). Then, the dominant and submissive groups were subcutaneously injected with Desipramine (25 micrograms/kg), anesthetized at a 60 min interval and injected with 5, 7-DHT into the left lateral ventricle (25 micrograms/25 microliters 0.9% NaCl). After a 30-day interval, both lesioned dominants and submissives were confronted to a different untreated intermediate subject over six daily sessions (postlesion scores). Differences between pre- and postlesion scores for all behavior studied were not found in dominant subjects. In submissive subjects, however, the postlesion scores of total aggression, defensive behavior, and emotional behavior were significantly higher than pre lesion scores. When brain 5-HT was assayed 60 days after injection about 34% depletion was found for both groups of pigeons. These findings suggest that the behavioral response to brain 5-HT denervation in pigeons is related to the behavioral characteristics of the subject previous to the lesion.

Effect of subchronic and chronic exposure to 5-hydroxytryptophan (5-HTP) on the aggressive behavior induced by food competition in undernourished dominant and submissive pigeons (Columba livia).

The acute administration of 5-HTP was reported to block in undernourished dominant pigeons the aggressive attacks induced in a submissive partner by food competition. In the present study, undernourished pigeons with previously consolidated dominance were submitted to subchronic and chronic 5-HTP treatment. Adult males (n = 28) were kept at 80% of their body weight by a restricted diet. These were divided in pairs made of a previously ranked dominant subject (total time spent in aggression higher than 200 s/20 min) and a submissive one of similar body weight (time spent in aggression between 90 and 150 s/20 min). The same pairs were exposed to a daily 20 min interaction during each experiment in an observation chamber bearing a central feeder. The time spent in aggressive behavior, feeder control behavior and eating behavior was recorded. Intratest body weight gain was also recorded. In Experiment 1, 8 pairs of pigeons were exposed to a daily trial for 4 successive days (pretreatment-scores). The dominant subjects were then injected subcutaneously, 30 min. before trials, with 7.5 mg/kg 5-HTP from day 5 to day 8 (Treatment scores). The Recovery scores were obtained through a 4-trial post-treatment schedule. In Experiment 2 different pigeons were used. The pretreatment and recovery scores were obtained according to a 16-trial schedule (16 days). Both 4-day (subchronic) and 16-day (chronic) 5-HTP treatments attenuated aggression by the dominant subjects and reduced their intra-test body weight gain but did not decrease dominance for feeder control. The recovery scores of total aggression in subchronic experiments returned to pretreatment scores. In chronic experiments, instead, the recovery scores of aggression remained lower than pretreatment scores, whereas body-weight-gain scores came back to pretreatment values. This suggests that dominant subjects submitted to chronic 5-HTP might have learned to maintain dominance and feeder control in a virtual absence of aggressive behavior.

La serotonina en el marco de las teorias integradoras de la depresión / Serotonin in the mark of integrated theory of depression

La teoría serotoninérgica (5-HT) postula que una hipofunción 5-HT cerebral constituye el principal mecanismo fisiopatogénico de la depresión. Consistentemente, el tratamiento crónico con antidepresivos (AD) induciría una hiperfunción 5-HT por desensibilización de los autoreceptores inhibitorios 5-HT1A y 5-HT1D. Sin embargo, mostramos que en modelos animales el déficit 5-HT provocado por lesiones difusas o lesiones del raphe no induce una reacción depresiva y que tampoco ha podido comprobarse que las acciones crónicas de los AD se deban a un aumento o a una disminución de la actividad 5-HT cerebral. Las teorías monoaminérgicas (MA) integradoras preponen que los tres sistemas MA (5-HT, noradrenérgico y dopaminérgico) están involucrados. Se basan en que cualquier variable experimental o farmacológica aplicada a uno de ellos afecta inmediatamente el funcionamiento de los demás. Se muestra que cada MA tendría su propia importancia relativa en relación con los diferentes componentes sintomáticos del cuadro depresivo. Las teorías MA integradoras no descartan la participación de otros transmisores y moduladores por lo que se incluye un comentario sobre la probable importancia de ACh, GABA y algunos neuropéptidos.

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 5-HTP and ketanserine on the aggressive reaction induced by food competition in dominant and submissive pigeons (Columba livia).

There is abundant literature about the effects of manipulation of 5-hydroxytryptamine (5-HT) systems on some killer behaviors as well as on social isolation and shock-induced aggression in rodents. In this work we have analyzed the effect of 5-HT manipulation on the aggressive behavior induced by food competition in undernourished pigeons. Adult males (n = 12) were caged individually and their body weight kept at 80-85% by a restricted diet. These were divided in pairs which were exposed daily to an aggressive interaction test (20 min) in a 1.5 x 1.5 x 2.0 m chamber bearing a central feeding device. Once consolidation of dominance was obtained in each pair, the dominant and the submissive members were injected subcutaneously, on alternating days, with 5-hydroxytryptophan (5-HTP) (7.5, 15 and 30 mg/kg), ketanserine (20 and 30 mg/kg) and a combination of ketanserine (20 mg/kg) and 5-HTP (7.5 mg/kg). Aggression was evaluated by scoring the frequency and time spent biting, wing beating, aggressive following and vocalizations, threatening and pushing the opponent in 20-min tests. The time spent running away was also scored. Intratest feeding was ascertained by weighing the subjects immediately before and after testing. The scores were compared with those obtained after saline injection on the preceding day (C-scores). 5-HTP (7.5 mg/kg) attenuated aggression without affecting feeding in dominant members, and decreased the time spent running away by submissives. Higher doses of 5-HTP decreased feeding but did not potentiate the anti-aggressive effects. The 5-HT2 antagonist, ketanserine did not affect aggression but decreased feeding at the dose of 30 mg/kg. Ketanserine injection clearly prevented the anti-aggressive effects of 5-HTP but caused a decrease of feeding. Results show that 5-HT stimulation in pigeons can preferentially block aggression in this particular experimental situation. It is suggested, in addition, that 5-HT2 receptors might be involved in such an effect.

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.

A further analysis of behavioral and endocrine effects of unpredictable chronic stress.

Tolerance can develop when rats are repeatedly exposed to some predictable stressors. This does not occur, however, when rats are exposed to unpredictable chronic stress. In this study we have analyzed some behavioral and endocrine effects in male and female rats treated daily with unpredictable emotional stressor (ES-groups) or unpredictable physical stressors (PS-groups) over a 14-day period. Animals were then submitted to three behavioral tests at 24 hr intervals. Experiment 1 shows that when rats were tested in an enriched environment both total motor activity and exploration of the novel object were impaired by the PS treatment. This suggests the occurrence of motivational deficit. The fact that the PS-groups also showed increased intratest defecation suggests increased emotionality. When animals were submitted to an emergence test the PS-groups showed longer emergence latency, lower frequency of emergencies and lower time spent exploring the emergence compartment than the ES- and the C-group. This strongly supports that the PS treatment increased emotionality in rats. When ES- and PS-groups were exposed to a forced swim test they showed longer immobility duration (despair reaction) but only the PS-group displayed lower frequency of jumps (escape reaction). Results of all tests performed revealed that females were more resistant than males to the behavioral effects of the PS treatment. The day after the behavioral testing was completed, basal levels of corticosterone and prolactin were investigated in male subjects. The PS-group showed higher baseline levels of these "stress labile" hormones than the ES and the C-group.(ABSTRACT TRUNCATED AT 250 WORDS)

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.