The interaction between β-[Tyr9]melanotropin-(9–18), haloperidol and amphetamine in different behavior tests of rats

The effects of β-[Tyr⁹]melanotropin-(9–18) on the extinction of the active avoidance reflex in (dopamine receptor blocker) haloperidol-treated animals, and on the open-field activity in haloperidol and amphetamine-treated rats were studied. It was shown that a systemically given 100 ωg dose of the peptide, which had no action on the ambulation and rearing activity in the open-field test, could still delay the extinction of the active avoidance reflex. Haloperidol treatment was able to partially block the effects of the ICV administered β-[Tyr⁹]melanotropin-(9–18) on both the extinction and open-field activity. After intracerebroventricular administration, the effect of the peptide on the open-field test was partially similar to that of amphetamine: it facilitated the ambulation and rearing activity, and (in contrast with amphetamine) was able to facilitate the grooming activity, even in the presence of amphetamine. The results suggest that dopaminergic innervation might play a mediating role in the effect of β-[Tyr⁹]melanotropin-(9–18) on the extinction of the active avoidance reflex and open-field activity. The effect on the open-field activity differens in part from that of amphetamine.     

Effects of prenatal alcohol consumption on open-field behaviour and alcohol preference in rats

Throughout gestation pregnant Wistar rats consumed a liquid diet containing sustagen and ethanol. Control mothers were fed on lab chow. Subsequently, the offspring of the ethanol-fed mothers displayed significantly greater activity (ambulation and rearing) in an open-field test. Further, pups whose mothers were exposed to ethanol consumed significantly more ethanol in a preference test, compared to control offspring.     

Long-term effects of prenatal phenytoin exposure on offspring behavior in rats

Pregnant Sprague-Dawley CD rats were administered phenytoin by gavage on days 7-18 of gestation in doses of 0 or 200 mg/kg. The offspring were tested at various ages to determine the duration of postnatal dysfunction and its replicability and generality compared to previous experiments. Phenytoin offspring had increased newborn (5.2%) and preweaning (16.7%) mortality compared to controls (0% and 3.1%, respectively), and an 8.5% reduction in average body weight at 28-70 days. No weight differences were significant at other ages. Phenytoin offspring showed increased activity on multiple tests, swam slower in a straight channel, committed more errors and took more time in the Cincinnati water maze, startled less, and had longer latencies on the Morris hidden platform test. Among phenytoin offspring 42.3% exhibited the abnormal circling defect previously described (14,17). Consequently, data were reanalyzed in terms of circlers, noncirclers, and controls to determine the contribution of this effect to the dysfunctions observed. Circlers accounted for the differences in open-field activity, figure-8 ambulation, hole-board horizontal locomotion, straight channel swimming time, water maze retention errors, tactile prepulse startle inhibition, and some trials of the Morris test. Circlers and noncirclers differed from one another and from controls on measures of figure-8 rearing, water maze errors and times, and some trials of the Morris test, with circlers more affected than noncirclers. Circlers and noncirclers did not differ from one another, but both differed from controls, on measures of early locomotion, hole-board vertical activity, and unmodified startle amplitude. Circling was hypothesized to reflect an underlying vestibular defect, however, the data also support the view that phenytoin has effects beyond those accounted for by possible vestibular effects.     

Prenatal cocaine exposure: effects on locomotor activity in rat offspring

This study examines the developmental effects of prenatal exposure to cocaine in the rat, evaluated during the first month of life through open-field behavior. The offspring of Wistar dams that received 60 mg/kg of cocaine, from gestational day 8 to 22, were examined in the open-field during the second, third and fourth weeks of postnatal life in three consecutive 15-min daily sessions, starting on postnatal day (PND) 14, (PND 14–16), PND 21 (PND 21–23) and PND 28 (PND 28–30). Results show that prenatal exposure to cocaine increased total activity and rearing behavior on PND 22 and PND 29. Also, on PND 14, cocaine-exposed animals reared significantly more than control rats. There were no significant differences in the frequency of center and peripheral ambulation, nor in the defecation rate. The present results evidence alterations in the emotional behavior of rats prenatally exposed to cocaine. The delayed onset of exploration in the open-field observed in cocaine-exposed animals suggests that they take more time to become habituated to a novel and open environment.     

Cannabinol and cannabidiol in combination: temperature, open-field activity, and vocalization

Rectal temperature as well as unconditioned activity in an open-field (O-F) arena, and palpation-induced vocalization were examined in rats treated intraperitoneally with cannabinol (CBN, 17.5 or 56 mg/kg) and cannabidiol (CBD, 10 or 30 mg/kg), either singly or in combination. CBN singly resulted in hypothermia which was not attenuated by the addition of CBD. CBN reduced ambulation and rearing activities as compared to vehicle-treated rats. CBD in combination with CBN did not attenuate these effects; the CBD doses in themselves appeared inactive. Vocalization occurred to a significantly greater extent in the CBN singly-treated rats as compared to the controls and the CBD singly-treated rats. Thus, CBD did not counteract the temperature and open-field effects induced by CBN. This is discussed in relation to previous results from drug discrimination experiments.     

Behavioral and developmental outcomes of prenatal and postnatal vanadium exposure in the rat.

The developmental and behavioral outcomes of uninterrupted exposure to vanadium was studied in the rat. Starting 3 days before birth and up to the 100th day of extrauterine life, rats received as drink either a water solution of vanadyl sulphate (300 mg l(-1)containing 70 mg l(-1)of vanadium element, which is equal to an ingested dose of about 10 mg kg(-1)per day of vanadium element) plus NaCl 5 g l(-1), or a water solution of NaCl 5 g l(-1), or plain water [up to weaning (25th day of extrauterine life) treatment was given to dams and offspring]. At weaning, survivors were fewer and body weight was found to be significantly lower in the offspring of vanadium plus NaCl-treated dams than in the offspring of the other two groups. After weaning, growth retardation continued to be significant in both vanadium plus NaCl- and NaCl-treated rats. Such an effect was more pronounced in males than in females. Locomotor activity--evaluated at 1 month of age--was not significantly different in the three groups of rats. In the open-field, male (but not female) vanadium plus NaCl-treated rats had a reduced outer ambulation, rearing posture and grooming activity, and an increased defecation, in comparison with the males of the NaCl group, and reduced rearing in comparison with control males. As concerns ingestive behaviors, the only significant datum was an increased water intake in NaCl-treated males. Finally, at the 100th day of life, working memory was significantly impaired in both vanadium plus NaCl- and NaCl-treated rats.     

Some analogs of Tyr-MIF-1 affect passive avoidance behavior but not motor activity in rats

The effects of three analogs of the brain peptide Tyr-MIF-1 (Tyr-Pro-Leu-Gly-NH2) were tested in several behavioral tests after peripheral injection in rats. In the passive avoidance test, rats injected SC with 1 mg/kg Ala-MIF-1 or Phe-MIF-1 entered the second compartment of two-chamber shuttle box significantly faster than did rats receiving diluent. Leu-MIF-1 failed to produce significantly faster entry compared to diluent. None of the peptides significantly affected ambulation, rearing, or defecation. Flinch and escape thresholds were not affected by Ala-MIF-1, the only analog tested for this behavior. The results demonstrate that some analogs of Tyr-MIF-1 can exert behavioral effects similar to those exerted by the parent compound whereas other analogs resemble MIF-1 in being inactive under these experimental conditions.     

Assessment of acute behavioral toxicity of low doses of diisopropylfluorophosphate (DFP) in rats.

The effect on behavior of single subtoxic doses (100 and 600 micrograms/kg i.p., i.e. 1/77 and 1/13 of LD50, respectively) of an organophosphorous compound, diisopropylfluorophosphate (DFP), was studied in male Wistar rats. In the open-field test, the lower dose of DFP tended to increase ambulation, while the higher dose showed a trend towards a decrease in ambulation, rearing and frequency of defecation. In the elevated plus-maze, rotarod, elevated bridges and hot plate tests, DFP-treated rats did not differ significantly from the olive oil-treated controls. DFP significantly impaired the performance of rats in the one-trial passive avoidance task and dose-dependently decreased spontaneous locomotor activity for 4 hours after administration. At the doses used DFP only slightly inhibited acetylcholinesterase activity in the blood and different brain areas. The results show that the higher dose of DFP had an inactivating effect on the behavior of rats, while the lower dose did not markedly change their behavioral pattern. Our findings indicate that anticholinesterase compounds, such as DFP, can alter behavior even after single small subtoxic doses.     

Effects of the CB1R agonist WIN-55,212-2 and the CB1R antagonists SR-141716 and AM-1387: open-field examination in rats

This study examined the open-field (O-F) effects in rats of the cannabinoid 1 receptor (CB1R) agonist WIN-55,212-2 (WIN; 1 to 5.6 mg/kg) and its interaction with the CB1R antagonist/inverse agonist SR-141716 (1 to 5.6 mg/kg). Additionally, separate studies examined the O-F effects of SR-141716 (1 to 10 mg/kg) and a newly synthesized CB1R selective antagonist/inverse agonist AM-1387 (3 and 10 mg/kg) when these ligands were administered alone. Both antagonists are characterized in vitro by decreased of GTPgammaS binding and increased cAMP accumulation (inverse agonism). WIN dose dependently reduced ambulation (horizontal activity) and rearing (vertical activity); SR-141716 completely (WIN 3 mg/kg) or partially (WIN 5.6 mg/kg) normalized these behaviors. WIN alone resulted in circling and in an increased latency to leave the start area of the O-F, effects blocked by all doses of SR-141716. Both the increased scratching and grooming, associated with SR-141716 administration, were attenuated but not abolished by WIN. SR-141716 alone tended to reduce ambulation (significant at 10 mg/kg) and rearing (non-significant), had no effect on latency, and increased scratching and grooming (both frequency and duration), at doses of 3 mg/kg and up. At the doses examined, AM-1387 had no effect on ambulation, rearing, latency but significantly increased scratching (10 mg/kg); there was also a trend for increased grooming (both frequency and duration). The O-F profile of WIN suggests more similarity with the effects of THC rather than methanandamide (and presumably also anandamide). Intrinsic activity (scratching and grooming) by SR-141716 was re-affirmed and seemed to be associated with administration of AM-1387 as well. AM-1387 was less potent than SR-141716.     

The effects of Parachlorophenylalanine and stimulus intensity on open-field test measures in rats

An inhibitor of 5-hydroxytryptamine synthesis, p-chlorophenylalanine (PCPA), or an inert saline solution was administered intraperitoneally to rats. At maximum depletion of serotonin (72 hr after injection), the rats were tested in the standard, four-day open-field test. A further four days of testing in the open field in which the sound level was raised from the standard 78 to 93 dB showed that, while PCPA increased defaecation in both sexes and under both sound levels, the controls increased defaecation at the higher level stimulus intensity, whereas PCPA-injected rats defaecated less. Parachlorophenylalanine increased ambulation in males on the first day of open-field testing but not in females. On the remaining seven days of testing PCPA markedly reduced ambulation in females but did not affect ambulation in males. Across-trial habituation of neither the defaecation nor the ambulation measure was influenced by PCPA.     

Neonatal 6-hydroxydopamine-induced dopamine depletions: motor activity and performance in maze learning

Three experiments were performed to study the effect of dopamine (DA) depletions, induced by neonatal intracerebroventricular (ICV) treatment with 6-hydroxydopamine (6-OHDA), upon measures of spontaneous motor activity. Instrumental learning for food reward in an Olton radial arm maze and escape learning from a large, circular water maze were studied also. Motor activity was measured by direct observation of rats in a modified radial arm maze and by use of automated test cages equipped with photocell devices. 6-OHDA-treated rats demonstrated considerable and long-lasting locomotor (ambulation) activity and total activity increases. 6-OHDA-treated rats showed notably less rearing activity than the vehicle-treated rats during the initial 20 min of each 60-min test period. However, over the second half of these 60-min test periods, the 6-OHDA-treated rats demonstrated significantly more rearing activity than the vehicle-treated rats. In the acquisition of the running response, to obtain the 8 food pellets placed in each of the 8 arms of the radial arm maze, 6-OHDA rats showed a retarded acquisition, as measured by the latency and number of arms visited to acquire all eight pellets. 6-OHDA-treated rats failed completely to acquire the Morris-type swim maze task by which they were required to locate a platform just under the water surface in a circular water tank. The neurochemical assays indicated severe DA depletion in several forebrain regions. The present findings add to existing indications of the potential of this DA depletion condition as an animal model of the minimal brain dysfunction syndrome.     

Dose-response effects of taurine on some open-field behaviors in the rat

In two experiments albino rats were injected i.p. with various doses of taurine and their subsequent behavior in an open-field apparatus was observed. Increasing doses of taurine significantly decreased ambulation levels, increased latency scores, and increased thigmotaxis (wall-hugging behavior). In general, 50 mg/kg or more of taurine was required to produce significant changes in the dependent behavioral measures. The open-field behaviors of rearing and defecation were not significantly affected by the drug manipulation. The results of these experiments suggest that taurine may act as modulating or stabilizing agent in the central nervous-motor system rather than as a diffuse inhibitory agent.     

Effects of short-term and long-term depleted uranium exposure on open-field behavior and brain lipid oxidation in rats

Male and female rats were exposed to depleted uranium acetate (DU) in drinking water at doses of 0, 75, or 150 mg/L for either 2 weeks or 6 months. After exposure, the animals were tested for behaviors in the open-field. After testing in the open-field, the brains were examined for levels of lipid oxidation using the thiobarbituric acid (TBA) assay. Behavioral differences (line crossing and rearing) were seen in male rats after 2 weeks exposure to DU in drinking water for the highest dose group. Increased brain lipid oxidation was seen for the highest dose group for both genders. Lipid oxidation levels correlated significantly with line crossing and rearing in the open-field. After 6 months exposure, behavioral differences for male rats in the open-field remained and expanded to include other behaviors (grooming, defecation, and urination). Female rats also demonstrated some behavioral changes after 6 months exposure. Lipid oxidation in the brain continued to be seen; however, these levels no longer correlated with open-field behaviors. These data suggest that DU is a toxin that crosses the blood-brain barrier, producing behavioral changes in male rats and lipid oxidation regardless of gender in as little as 2 weeks in the rat. Longer exposures to DU may produce greater behavioral changes but compensatory mechanisms may reduce the effects of lipid oxidation. Males appear to be more sensitive to the behavioral effects of DU.     

Within-session behavioral decrement of atypical antipsychotics: Role of novelty

In order to gain a better understanding of the characteristics of antipsychotic-induced within-session decrements in unconditioned behavioral responses of mice, and whether they are sensitive to novel environmental stimuli, we studied the acute effects of haloperidol and atypical antipsychotic drugs (sulpiride, thioridazine, clozapine, and remoxipride) in familiar and novel open-field conditions in mice. The results show that familiarized controls and antipsychotic-treated groups had a progressive reduction in ambulation and rearing during the 10-minute open-field session. By manipulating the configuration of the open-field situation, familiarized controls as well as mice treated with typical or atypical antipsychotic drugs were able to exhibit an enhanced response to the presentation of novel stimuli. It may be noted that both the maintenance and the initiation of ambulation were affected by antipsychotic treatment. Furthermore, when comparing novel versus familiar groups during the 10-minute session, the increase in ambulation induced by atypical antipsychotic treatment was maintained longer (6–8 minutes) than that induced by haloperidol (4 minutes). In summary, these findings show that an important feature in the reinstatement of both typical and atypical antipsychotic-induced behavioral decrement may be a change in the stimulus conditions. Drug Dev. Res. 42:71–75, 1997. © 1997 Wiley-Liss, Inc.     

Effects of alpha methyltyrosine and parachlorophenylalanine on open field behavior in rats given tranylcypromine stereoisomers and lithium carbonate.

Parachlorophenylalanine (PCPA) and alpha methyltyrosine (AMT) were used to study the roles of serotonin and catecholamines in hyperactivity produced by the stereoisomers of Tranylcypromine (d-Tc and 1-Tc) in male Wistar rats fed a normal diet (control groups) or a diet containing lithium carbonate (lithium groups). Components of locomotor activity were measured in an open field. Lithium decreased ambulation. d-Tc increased ambulation and caused jerky side-to-side movements. PCPA and AMT prevented the effects of d-Tc on ambulation while only PCPA prevented the effects of d-Tc on movement. 1-Tc increased ambulation. The effects of 1-Tc on ambulation were potentiated by PCPA and prevented by AMT. Rearing was increased by 1-Tc and d-Tc in rats given lithium. PCPA and AMT prevented the effects of 1-Tc and d-Tc on rearing in lithium groups. The findings suggest that the roles of serotoninergic and catecholaminergic mechanisms differ for components of open field behavior in control rats and rats given lithium.     

Dose-response analysis of the effects of buspirone on rearing in rats

The effects of buspirone were tested on rearing in an open field. Six different doses of buspirone (10, 3.3, 1.1, 0.3, 0.1 and 0.04 mg/kg) and a single dose of chlordiazepoxide (5 mg/kg) were administered i.p. to separate groups of rats. Buspirone produced a dose-dependent decrease in rearing in the range 0.04-10 mg/kg, whereas only the higher doses (10 and 3.3 mg/kg) decreased ambulation significantly. Chlordiazepoxide reduced rearing to an extent equivalent to 1 mg/kg of buspirone. Together with data in the literature, the results suggest that 5-HT1A agonists affect rearing at lower doses than ambulation; that the effects of buspirone in the open field are similar to classical anxiolytics; and that changes in rearing may be more closely related to anxiolytic than muscle relaxant, anti-convulsant and other GABA-mediated effects of the classical anxiolytics.     

Behavioral alterations induced in rats by a pre- and postnatal exposure to 2,4-dichlorophenoxyacetic acid.

The purpose of this study was to determine whether the behavioral development pattern was altered by a pre- and postnatal exposure to 2,4-Dichlorophenoxyacetic acid (2,4-D). Pregnant rats were daily orally exposed to 70 mg/kg/day of 2,4-D from gestation day (GD) 16 to postnatal day (PND) 23. After weaning, the pups were assigned to one of the two subgroups: T1 (fed with untreated diet until PND 90) and T2 (maintained with 2,4-D diet until PND 90). Effects on offsprings were evaluated with a neurotoxicological test battery. Neuromotor reflexes, spontaneous motor activity, serotonin syndrome, circling, and catalepsy were analyzed during various postnatal ages. 2,4-D neonatal exposure induced delay of the ontogeny of righting reflex and negative geotaxis accompanied by motor abnormalities, stereotypic behaviors (excessive grooming and vertical head movements), and hyperactivity in the open field. Adult rats of both sexes (T2 group) showed a diminution of ambulation and rearing, while excessive grooming responses were only observed in T2 males. Besides, these animals manifested serotonin syndrome behaviors, catalepsy, and right-turning preference. Some behaviors were reversible, but others were permanent, and some were only expressed after pharmacological challenges.     

Acute and chronic nicotine effects on measures of activity in rats: a multivariate analysis

Nicotine has been reported to increase or decrease measures of activity in rats, including locomotor activity and rearing. Nicotine dose and repeated exposure to nicotine are known to be important factors in determining the effects on locomotor behavior. Less information has been gathered on rearing and other measures of activity. Rats were tested repeatedly, once per day, in Digiscan automated activity analyzers that reported 19 measures of activity. Each rat was given the same drug and dose each day, either saline or 0.1, 0.2, or 0.4 mg/kg nicotine. The 19 measures were combined or modified to produce 14 measures that were examined using factor analysis to help select the most independent measures. Four measures were selected to describe the effects of dose and to compare day 1 results with day 5 results. Total distance moved was increased in a dose-related fashion and was greater on day 5 than on day 1. Rearing was increased at low doses and decreased at high doses on both days. Stereotypy was increased approximately the same amount by all three doses, and was greater on day 5 than on day 1. Center time was increased by the highest dose on both days. These results once again point out the influences of repeated testing and repeated nicotine exposure on behavior. They may also help to clarify why some studies have reported that both ambulation and rearing are increased after nicotine whereas others find opposite effects.     

Automated multivariate measurement of spontaneous motor activity in mice: time course and reliabilities of the behavioral measures

A variety of automated procedures have been developed to measure certain aspects of spontaneous motor activity in small animals. The present study used a Digiscan Animal Activity Monitor to measure six different aspects of spontaneous motor behavior in male CF-1 mice. The Digiscan system uses infrared beams and computer analysis to quantify various behavioral variables. The mice were tested for 1 hour on 2 different days of the week for 3 consecutive weeks. Both the temporal changes in the measured variables and the test-retest reliabilities were examined in a group of 30 mice. Statistical analysis of the data revealed significantly higher mean values for total movement time, average distance travelled, and horizontal activity on the first test session relative to the second session (p less than 0.01). The other 3 measures, total distance travelled, number of movements, and average speed, did not vary significantly across test sessions. All 6 behavioral variables showed good test-retest reliabilities and these could be increased by aggregating the data on a weekly basis. The present results indicate that the measures obtained from the Digiscan system are reliable and that the animals should first be habituated to the test apparatus in order to obtain stable baseline activity values.