Evaluation of the acute effects of amitriptyline and fluoxetine on anxiety using grooming analysis algorithm in rats

The tricyclic amitriptyline and the selective serotonin reuptake inhibitor fluoxetine have distinct actions in animal models of anxiety, though both antidepressants are used against anxiety disorders. Grooming behavioural sequencing, rather than its general "activity" measures, has been suggested to measure effectively the pharmacologically induced anxiolytic and anxiogenic-like effects in rats and mice. In the present study, the acute effects of amitriptyline and fluoxetine on anxiety were re-evaluated by using an analysis algorithm in novelty-induced grooming activity in rats. Additionally, the effects on anxiety-like behaviour in the hole board were examined. Amitriptyline (5 and 10 mg/kg) and fluoxetine (5 and 10 mg/kg) not only affected the traditional gross measures, but also produced changes in incorrect transitions and regional distribution of grooming behaviour. High dose of fluoxetine showed an anxiogenic-like profile by reducing head dipping and rearing in the hole board. Depending on the effects on the behavioural microstructure of grooming activity, present findings imply that amitriptyline may possess anxiogenic and fluoxetine may possess anxiolytic activities. However, measures of hole board do not fully support this suggestion.     

Cocaine-conditioned behavioral effects: a role for habituation processes

Cocaine has potent locomotor stimulant effects in rodents, which seemingly can become conditioned to test environment cues. In two experimental protocols, we measured the effects of cocaine on locomotor activity and grooming behavior, and subsequently tested whether these cocaine effects became conditioned to contextual cues. In the first experiment, three groups of rats received 14 injections of either saline or cocaine (10 mg/kg) paired or unpaired to the test environment. Cocaine increased locomotion and decreased grooming during treatment and on the conditioning test. Over the course of the treatment phase, however, the saline- and cocaine-unpaired groups but not the cocaine paired group developed progressively lower locomotion and higher grooming scores indicative of substantial habituation effects. To examine whether the cocaine may have impaired the acquisition of habituation effects rather than induce a Pavlovian cocaine conditioned response, an additional experiment was conducted in which two additional non-habituation saline and cocaine control groups were added to the experimental design. On a conditioning test, the two non-habituation control groups were equivalent in activity and grooming behavior to the cocaine-paired group. The findings were consistent with a failure by cocaine-paired animals to acquire habituation effects, which could transfer to the non-cocaine state. The connection between cocaine and novelty/habituation may have substantial importance for understanding cocaine effects.     

Evidence for Pavlovian conditioning of cocaine-induced responses linked to emotional behavioral effects

The pairing of cocaine treatments with a specific test environment typically leads to cocaine-conditioned drug effects. In this study, we first pre-exposed rats 10 times to an open-field environment to establish an habituation asymptote in locomotor activity prior to the initiation of cocaine treatments. Two groups (N=10) equated for locomotion, grooming, central zone penetrations and rearing behavior were used. One group received five pairings of cocaine (10.0 mg/kg) and the second group five pairings of saline injections with placements in the open-field environment. Subsequently, both groups received a saline test to detect possible cocaine-conditioned behavioral effects. During the cocaine treatment phase, cocaine enhanced locomotion and central zone penetrations but decreased rearing and grooming. On the conditioning test, the cocaine group exhibited enhanced central zone penetrations and decreased grooming as compared to the saline group. There were no group differences in locomotion or rearing. When within group comparisons were performed between behavioral responses on the pre-conditioning test vs. the conditioning test, the saline group scores were essentially unchanged. In contrast, the cocaine group exhibited higher central zone penetrations and decreased grooming without changes in locomotion or rearing. In that a cocaine conditioning test can also be viewed as a cocaine withdrawal test, two additional experiments were conducted using an unpaired conditioning protocol to test for withdrawal effects without conditioning. These results indicated that the central zone and grooming effects observed in the conditioning protocol were not withdrawal effects. Altogether, these findings provide support for Pavlovian conditioning of cocaine-induced changes in emotion-related behavioral responses.     

Ameliorative potential of sodium cromoglycate and diethyldithiocarbamic acid in restraint stress-induced behavioral alterations in rats

The present study was designed to investigate the ameliorative effects of sodium cromoglycate and diethyldithiocarbamic acid in acute stress-induced behavioral alterations in rats subjected to restraint stress. The rats were placed in the restrainer (5.5 cm in diameter and 18 cm in length) for 3.5 h. Restraint stress-induced behavioral alterations were assessed using the hole-board, social interactions and open field tests. Restraint stress resulted in a decrease in the frequency of head dips, rearing in the hole board, line crossings and rearings in the open field, and an increase in avoidance behaviors in the social interaction tests. Sodium cromoglycate (25 mg/kg and 50 mg/kg, ip), a mast cell stabilizer, and diethyldithiocarbamic acid (75 mg/kg and 150 mg/kg, ip), a selective NF-κB inhibitor, were employed to modulate restraint stress-induced behavioral changes. The administration of sodium cromoglycate and diethyldithiocarbamic acid significantly attenuated the restraint stress-induced behavioral changes. The noted beneficial effects of sodium cromoglycate and diethyldithiocarbamic acid may possibly be attributed to mast cell stabilization and inhibition of NF-κB activity, respectively.     

The effects of CRF and α-helical CRF on anxiety in normal and hypophysectomized rats

The effect of corticotrophin-releasing factor (CRF) on anxiety in normal and hypophysectomized (HYPOX) rats was investigated. Intracerebroventricular injection (i.c.v.) of 2 μg of CRF increased anxiety in the elevated plus maze test in normal and HYPOX rats. Anxiety was measured as the ratio of time spent in the open arms of the maze to total time spent in all arms of the maze. CRF also reduced head dipping and rearing in the hole board, and the number of entries into the arms of the plus maze. These latter changes in behavior were independent of the changes in anxiety. All behavioral effects of CRF in HYPOX rats were blocked completely by the CRF receptor blocker, α-helical CRF (50 μg). Completeness of hypophysectomy was assessed by measuring plasma corticosterone (CORT) level changes 20 min after i.c.v. CRF (2 μg). CORT levels of all HYPOX rats given CRF were well below (< 1/10th) resting baseline levels of normal rats. Moreover, i.c.v. injection of saline vehicle nearly tripled CORT levels over resting baseline in normal rats, and CRF increased CORT levels 2-fold over vehicle. Taken together, these findings replicate the observation that CRF administered i.c.v. to rats is selectively anxiogenic in the elevated plus maze. They also indicate that the anxiety produced by CRF does not involve activation of the pituitary-adrenal axis. Rather, CRF-induced anxiety depends on the binding of CRF to central nervous system CRF receptors. Finally, the plasma CORT data indicate that i.c.v. injection of saline vehicle is stressful, as is injection of CRF.     

8-OHDPAT effects upon cocaine unconditioned and conditioned behaviors: a role for drug stimulus effects

The effects of the 5-HT1A agonist, (+/-)-8-hydroxy-dipropylaminotetralin (8-OHDPAT) upon the unconditioned and conditioned behavior induced by cocaine were assessed in rats. Separate groups (n=7) received saline, cocaine (10 mg/kg), 8-OHDPAT (0.2 mg/kg), or 8-OHDPAT (0.2 mg/kg) plus cocaine (10 mg/kg) for eight treatment sessions (two per week) in which the rats were tested for 20 min in an open-field. On the eighth treatment session, cocaine enhanced locomotion and rearing but decreased grooming. 8-OHDPAT also decreased grooming and, when given in combination with cocaine, enhanced locomotion but attenuated cocaine-induced rearing. The two 8-OHDPAT groups differed substantially from each other and from the cocaine group in terms of locomotion during the drug treatment phase. Subsequently, all groups received a series of conditioning tests in which they received saline, 0.1, 0.2, or 0.4 mg/kg 8-OHDPAT prior to testing. Groups which had received either 8-OHDPAT or cocaine prior to the conditioning tests exhibited equivalent conditioned effects on the saline conditioning test. When conditioning tests were conducted with 8-OHDPAT, however, only the group which had previously received the combined 0.2 mg/kg 8-OHDPAT plus cocaine treatment exhibited a conditioned response and this effect only occurred at the 0.2 8-OHDPAT dose level. These observations indicate the important influence of the stimulus properties of drugs for the study of drug conditioning and for understanding drug interactions with cocaine.     

Effects of 5-HT-1A receptor agonists on CRF-induced behavior

Buspirone (2.0 or 4.0 mg/kg) and 8-hydroxy-2-(di-N-propylamino)-tetralin (8-OH-DPAT) (0.25 or 0.5 mg/kg) were used to examine the effects of serotonin 1A receptor agonists on the behavioral response of rats to centrally administered corticotropin-releasing factor (CRF). Behavioral observations were done with animals in their home cages. Parameters measured included locomotor activity, grooming and food consumption. CRF alone increased locomotor activity. 8-OH-DPAT also increased locomotion in both saline control and CRF-treated rats. Buspirone had no effect on basal locomotion or on CRF-induced hyperactivity. Both buspirone and 8-OH-DPAT antagonized CRF-induced grooming. Food consumption by fasted rats was suppressed by ICV CRF. 8-OH-DPAT suppressed eating by both ICV CRF and ICV saline-treated animals, while buspirone was without effect. These results demonstrate differences between the two putative 5-HT-1A agonists in their effects on CRF-induced behavior but also demonstrate that both suppress CRF-induced grooming.     

Pharmacological and genetic influences on hole-board behaviors in mice

Head dipping on a hole-board is frequently used as an indicator of exploratory tendencies in rodent studies. Drugs with diverse pharmacological properties alter head dipping suggesting that many neurotransmitter systems are involved in the expression of exploratory behavior. The aim of the current experiments was to determine the effects of several drugs from different classes on head dipping, and to compare the effects of some of these agents in lines of mice that have been selectively bred for divergent expression of head dipping on a hole-board. In the current experiments, the effects on head dipping of three doses each of fluoxetine, desipramine, GBR-12909, methamphetamine, pentylenetetrazol, and diazepam were evaluated in genetically heterogeneous mice. Most drugs altered the number of head dips in a predictable manner, but the effects on locomotion were generally as large as those seen for head dipping. Locomotion could completely account for the effects of fluoxetine and pentylenetetrazol, and to a lesser extent, diazepam. We have also developed replicate lines of mice selectively bred for high (High Exploratory Behavior: HEB) or low (Low Exploratory Behavior: LEB) head dipping on a hole-board and evaluated the effects of diazepam and methamphetamine on hole-board behaviors in these mice. Diazepam increased head dipping and locomotion equivalently in both lines of mice, but methamphetamine stimulated locomotion in HEB mice more than in LEB mice. These results broadly suggest that the effects of most drugs we tested are not specific for head dipping, since almost all drugs tested affected head dipping and locomotion equivalently. However, the results with the genetically heterogeneous mice and HEB and LEB mice suggest that some aspects of the dopaminergic system are involved in head dipping.     

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.     

Intrastrain variations in anxiolytic effect of nitrazepam in mice

This study investigated the individual differences in the baseline anxiety and anxiolytic effect of nitrazepam in Balb/c mice. Initially mice were sorted according into low, intermediate and high anxiety groups (LA, IA and HA) based on the number of entries to and time spent in open arms in elevated plus maze. Later, anxiolytic effect of nitrazepam (2 mg/kg, p.o) in LA, IA and HA mice was evaluated using hole board and light/dark tests. In Hole board test, LA mice made more number of head dippings and spent more time during head dippings, while HA mice made less number of head dippings and spent less time during head dipping when compared to that of IA mice. In light/dark test LA mice made more reentries to and spent more time in bright compartment, while HA mice made few reentries to and spent less time in bright compartment. Results suggest that mice of a single strain differ in their baseline anxiety and anxiolytic effect of nitrazepam.     

Effect of 5-HT1A agonists on stress-induced deficit in open field locomotor activity of rats: evidence that this model identifies anxiolytic-like activity

Deficits in locomotion and exploratory behaviour in an open field were induced in rats by restraint for 2 hr, 23 hr before testing. Diazepam, 0.62 and 1.25 mg/kg, intraperitoneally (i.p.), 15 min before testing, reversed the stress-induced reduction in locomotion; 1.25 mg/kg also attenuated the effect of stress on exploration (rearing and object exploring). Diazepam did not affect the activity of controls. A putative anxiogenic compound, pyrazoloquinoline (CGS 8216, 10 mg/kg administered 30 min before testing), also markedly reduced locomotion and exploration and the effect was reversed by 2.5 mg/kg diazepam, 15 min before testing. Buspirone, 0.1 mg/kg subcutaneously (s.c.) 15 min before testing, significantly attenuated the effect of stress on locomotion and exploration but had no effect in controls. Larger doses (0.5 and 1.0 mg/kg) markedly reduced the behavioural measures in controls and did not modify or enhance the effect of stress. 8-Hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT), 0.25 and 0.5 mg/kg (s.c.), 1 hr before testing, significantly attenuated the reduction in locomotion without affecting rearing and object-exploring in stressed rats. At doses from 0.125 to 0.5 mg/kg, 8-OH-DPAT reduced exploration in control rats. Two hr after restraint (corresponding to 21 hr before testing in the open field) 8-OH-DPAT, 0.125 to 2 mg/kg (s.c.), did not modify the open field deficits, caused by stress. In these treatment conditions, 0.5 and 2 mg/kg 8-OH-DPAT reduced locomotion and exploration in control rats.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of dopamine D1 and D2 receptor agonists and antagonists on bombesin-induced behaviors

Central administration of bombesin elicits excessive grooming and locomotor activity in rats. This grooming activity is one characterised by vigorous scratching of the face, nape and body flanks. Pretreatment with the D1 receptor antagonist SCH 23390 inhibited the expression of bombesin-induced activity with grooming being more inhibited than locomotion. Blockade of D2 receptors with eticlopride significantly attenuated the behavioral responses to bombesin. When SCH 23390 and eticlopride were administered concurrently, it was apparent that D1 blockade had a greater effect on grooming and D2 blockade a larger effect on locomotion. Stimulation of D1 receptors by SKF 38393 elicited non-stereotyped locomotor activity and a form of grooming behavior characterised by vigorous washing of the face and ventral body surfaces. Co-administration of bombesin and SKF 38393 resulted in a form of grooming which resembled that elicited by SKF 38393 alone. The specific D2 agonist PPHT elicited a form of locomotion characterised by a downward oriented head posture and slow ambulatory activity around the cage perimeter. Co-administration of PPHT and bombesin resulted in a complete suppression of bombesin-induced behaviors and was largely indistinguishable from activity observed under PPHT alone conditions. These data implicate both D1 and D2 receptor based mechanisms in the modulation/mediation of the behavioral effects of bombesin. Part of the bombesin-induced behavioral effects may be explained by (indirect) activation of (a) dopamine system(s).     

Time course of certain behavioral changes after hippocampal damage and their alteration by dopaminergic intervention into nucleus accumbens

Independent groups of rats with hippocampal, neocortical, or sham lesions were observed 7, 14, or 28 days after surgery in an open field-hole board apparatus and in a smaller circular apparatus. In the circular apparatus, animals were observed after unilateral injection of the dopamine agonist, 3,4-dihydroxy-phenylamino-2-imidazoline (DPI) or saline into nucleus accumbens. Behavioral changes in locomotion, exploration and grooming measured in the open field were consistent with those found previously after hippocampal damage, with each behavioral anomaly demonstrating a specific pattern of change after surgery. In general, the injection of DPI into nucleus accumbens produced greater behavioral change in animals with hippocampal damage than in animals with either neocortical or sham lesions. The drug-induced changes in the hippocampally lesioned rats made their behavior more like that of control animals. These results suggest that destruction of the hippocampus may induce alterations in dopaminergic mechanisms in nucleus accumbens which can be modified by appropriate pharmacologic intervention.     

The effects of convulsant and anticonvulsant treatments on the behavioural effects of ultrasound presentation in Lister hooded rats

Lister hooded rats exhibit bursts of locomotion when exposed to a 20 kHz acoustic stimulus; this ultrasound-induced locomotion has been suggested as a potential model for panic attacks. The present studies determined the effects of treatment with the convulsant agents strychnine and pentylenetetrazole and the anticonvulsant agents pentobarbital and ethosuximide on locomotor behaviour elicited by experimenter-presented ultrasounds in Lister hooded rats. Behaviour in a circular arena was viewed live and tracked electronically. In Experiment 1, brief exposure to an ultrasound stimulus typically resulted in short intensity-related bursts of locomotion in control rats. Pentobarbital or ethosuximide treatment reduced this short-term ultrasound-induced locomotion in a dose-related manner, whereas pentylenetetrazole or strychnine treatment increased these locomotor bursts. In Experiment 2, exposure to the ultrasound stimulus for a longer period resulted in irregular cycles of bursts of locomotion followed by periods of relative inactivity in control rats. In addition, approximately 10% of control rats exhibited convulsions associated with this long-duration ultrasound exposure at 98 dB sound pressure level. Sub-convulsant doses of the convulsant treatments increased the frequency of occurrence of convulsions associated with the ultrasound stimulus; pentobarbital or ethosuximide pretreatment significantly reduced this effect. The present findings suggest that a relationship exists between ultrasound-induced locomotor bursts and convulsant activity.     

Involvement of both opiate and catecholaminergic receptors in the behavioural excitation provoked by thyrotropin-releasing hormone: comparisons with amphetamine

Following direct administration of thyrotropin-releasing hormone (TRH), but not thyroid-stimulating hormone (TSH) or vehicle solution, into the lateral cerebral ventricle in rats, three main categories of behaviour were provoked: activity of the normal type--stimulation of forward locomotion, head and body rearing (as shown by an enhancement in gross movements); stereotyped activity--increased grooming and head swaying (as shown by an enhancement in fine movements); abnormal behaviour--tail elevation and piloerection (as observed grossly). The behavioural excitation caused by TRH was antagonized by pretreatment of the rats with either a narcotic receptor antagonist, naloxone, an alpha-adrenergic receptor antagonists, yohimbine, or a dopaminergic receptor antagonist, haloperidol, but not with a beta-adrenergic receptor antagonist, propranolol. Intraventricular administration of amphetamine to rats caused stimulation of forward locomotion, head and body rearing, increased grooming and sniffing. Unlike TRH, amphetamine did not produce wet-dog shakes, tail elevation and piloerection. Furthermore, the amphetamine-induced excitation was antagonized by pretreatment with a dopaminergic receptor antagonist, haloperidol, but not with either naloxone, yohimbine or propranolol. The data indicate that both opiate and catecholaminergic receptors are involved in the TRH-induced behavioural excitation, whereas dopaminergic receptors are involved in amphetamine-induced excitement in the rat.     

Effects on spontaneous and cocaine-induced behavior of pharmacological inhibition of noradrenergic and serotonergic systems

Cocaine-induced increases in dopamine (DA) contribute importantly to cocaine effects on behavior but, the role of concomitant increases in norepinephrine (NE) and serotonin (5-HT) is less well understood. In order to selectively block the increases in NE and 5-HT evoked by cocaine, autoreceptor preferring low doses (0.01, 0.025 and 0.05 mg/kg) of the a2 agonist, Clonidine or the 5-HT1A agonist, 8-OHDPAT were given as pretreatments 20 min prior to saline or cocaine (10.0 mg/kg) in separate groups of rats (N=10). With pharmacological stimulation of NE and 5-HT autoreceptors, release of these neurotransmitters would be suppressed and, therefore, less available for re-uptake blockade by cocaine. With increasing dose levels, Clonidine had marked inhibitory effects on spontaneous and cocaine-induced locomotion, grooming and rearing. 8-OHDPAT pretreatment also suppressed spontaneous locomotion, grooming and rearing; but, in contrast, did not reduce the cocaine locomotor stimulant effects. 8-OHDPAT, however, did suppress central zone entry and rearing in cocaine treated rats. Using ex vivo methods, we found that 8-OHDPAT selectively reduced 5-HT metabolism in the medial frontal cortex (MFC) and subcortical limbic brain. Clonidine selectively reduced NE metabolism in the MFC, but decreased both DA and 5-HT metabolism in the subcortical limbic brain without affecting NE metabolism. This diverse and broad spectrum of Clonidine effects upon neurotransmitters and behavior is striking and points-up the important, complex and integrative role of NE in brain function. While both Clonidine and 8-OHDPAT can substantially attenuate a number of cocaine behavioral effects, these inhibitory effects appear to be secondary to reductions in the behavioral baseline rather than reversals of cocaine effects.     

A protease inhibitor against acute stress-induced visceral hypersensitivity and paracellular permeability in rats

In the present study, we investigated the effects of camostat mesilate (CM), a synthetic protease inhibitor, on visceral sensitivity and paracellular permeability induced by the acute restraint stress. We also explored the possible mechanisms underlying these effects. The acute restraint stress was induced by wrapping the fore shoulders, upper forelimbs and thoracic trunk of Sprague–Dawley rats for 2 h. Either CM (30, 100 and 300 mg/kg) or saline was intragastrically administrated to the rats 30 min before the acute restraint stress. Visceral perception was quantified as visceral motor response with an electromyography in a subset of rats. Paracellular permeability was determined in another subset of rats. We found that the visceral sensitivity and paracellular permeability were significantly reduced in the CM-treated rats. Moreover, the fecal protease activity was decreased in the CM-treated rats. The ZO-1 protein expression was markedly reduced by the stress treatment, but this decrease was suppressed by CM administration. Our data indicated that CM could efficiently inhibit visceral sensitivity and paracellular permeability induced by the acute restraint stress in rats. Therefore, CM might be an effective drug for the treatment of irritable bowel syndrome.     

An assessment of the spontaneous activity of rats administered morphine,phencyclidine, or nicotine using automated and observational methods

The effects of morphine, phencyclidine, and nicotine on motor activity in rats were characterized using both observational and automated methods. Activity was scored observationally using a time-sampling method that tabulates discrete response categories (still, locomotion, rearing, sniffing, licking, gnawing, head down, swaying, grooming, falling). Behavior was assessed automatically using an activity monitor that records both the time and activity counts spent in large and small (less than 3 cm) movements, rearing, and resting. The following results using male Sprague-Dawley rats represent significant differences from saline-treated controls. Morphine (1–4 mg/kg SC) increased the incidence of locomotion, sniffing, swaying, and grooming depending on the time after drug injection. These changes corresponded to an increase in large and small movement counts and time as measured by the activity monitor. Phencyclidine (1.25–5 mg/kg SC) caused dose-related increases in the incidence of locomotion, sniffing, swaying, and falling, and induced greater large and small activity movement counts and time especially after the 5 mg/kg dose. Nicotine (0.033–0.33 mg/kg SC) decreased the incidence of rearing and increased the frequency of sniffing and grooming. These changes corresponded to a decrease of rearing activity and to a slight increase in small activity. The present data indicate that morphine, phencyclidine, and nicotine exert dose-related and time-related appearances of various categories of behavior in the rat, and that the data from the automated method complement the findings of the direct observational method.     

Selective antagonism by clonidine of the stereotyped and non-stereotyped motor activity elicited by atropine

The effects of clonidine, an indirectly-acting cholinergic antagonist, on 5 behaviors elicited by atropine (locomotion, rearing, sniffing, grooming and gnawing) were studied in rats. Clonidine did not alter the prevalence or magnitude of atropine-elicited locomotion and rearing. In contrast, clonidine suppressed the occurrence and degree of 3 stereotyped behaviors, namely, sniffing, grooming and gnawing. This selectivity of clonidine suggests differences in the neural pathways subserving the various stereotyped motor activities.     

The abnormal open-field behavior of SART-stressed rats and effects of some drugs on it

As part of an investigation on the behavioral characteristics of SART-stressed animals, an animal model of autonomic imbalance, the open-field behavior of SART-stressed (repeated cold-stressed) rats was studied and compared with that of rats exposed to other types of stress. In addition, the effects of several drugs on it were also studied. As compared with normal rats, SART-stressed rats exhibited increased locomotor activity, rearing and center-field penetration, together with decreased grooming and increased defecation, whereas they showed no significant changes in spontaneous movements in the daytime as measured by an Animex activity meter. These behavioral abnormalities were remarkably different from those due to 1-hr cold, 48-hr cold and repeated restraint stresses. These abnormal forms of open-field behavior due to SART stress were considerably inhibited by chlorpromazine, imipramine and neurotropin at doses having no corresponding influence on normal rats; and they were partially inhibited by alprazolam, diazepam and carpipramine at doses exerting considerable influence on normal rats. The above results show that SART-stressed rats exhibit open-field behavioral abnormalities that are different from those of rats exposed to other types of stress. Such abnormalities include excessive activity, which is considered to be caused by excessive emotionality.