Directional running in mice: effects of cocaine and chlorpromazine

Mice ran in a circular runway. Some received milk at every third circuit in a designated direction, clockwise or counterclockwise, in daily 1000-s sessions. Under control conditions, about 10 times as many circuits were made in the reinforced direction as in the non-reinforced direction. Cocaine (10, 30, 100 µM/kg) had little effect on the total number of circuits, but progressively increased the number in the non-reinforced direction. Chlorpromazine (1, 3, 10, 30 µM/kg) caused a monotonic decrease in total number of circuits and in number in non-reinforced direction. At the highest doses the proportion in the non-reinforced direction was increased. Mice, untrained in the runway and with no reinforcement of circuits in either direction, made many fewer total circuits than when running was reinforced and about equal numbers were in clockwise and in counterclockwise directions. Cocaine greatly increased the total number of circuits. As in the subjects whose running was reinforced, cocaine led to a much higher tendency for mice to run in a single direction. The similarities between the tendency to run in one direction after cocaine and the rotational behavior of rodents seen after cocaine and amphetamine suggest a common mechanism.     

Different effects of apomorphine on climbing behavior and locomotor activity in three strains of mice

Apomorphine (0.1, 0.25, 0.5, 1, 3 mg/kg, SC), induces a dose-dependent reduction of locomotor activity in DBA/2(DBA) and BALB/c(BALB) mice, while it enhances locomotor activity in a biphasic way in C57BL/6(C57) mice. On the other hand, apomorphine is ineffective in modifying climbing behavior in DBA mice while it increases climbing behavior in C57 and BALB mice. The results, taken together, suggest that these are two different behaviors, possibly controlled by different dopaminergic mechanisms depending on the genetic makeup.     

Variation in effects of nicotine in four strains of rats

Summary Male and female rats of Maudsley Reactive and Non-Reactive, Roman High and Low Avoidance strains were injected with either 0.8 mg/kg dose of nicotine bitartrate or distilled water. Nicotine facilitated rearing frequency. Strain differences were found. The Roman High Avoidance and Non-Reactive strains were more sensitive to nicotine than their counterparts. Female rats were found to be superior to the males in rearing score.The experimental work was done at the Institute of Psychiatry, London. The author is indebted to Dr. H. C. Holland, Director of the Animal Psychology Laboratory, for providing the laboratory facilities.     

Comparative extrapyramidal effects of Rauwolfia vomitoria, chlorpromazine and reserpine in mice

Most antipsychotics interfere with the dopaminergic system, resulting in extrapyramidal effects. This study compared the extrapyramidal effects of chlorpromazine (Cpz), the herb Rauwolfia vomitoria (RV) and its alkaloid reserpine (Res), used as antipsychotics, in mice. Ninety age-matched male CD-1 strain of mice (25?C33?g body weight) were divided into 3 groups, each consisting of 5 subgroups (n?=?6). Cpz (0.0, 0.25, 1.0, 2.0 and 4.0?mg/kg, i.p.) was administered 30?min before testing. RV (0.0, 0.25, 1.0, 2.0 and 4.0?mg/kg, i.p.) and Res (0.0, 0.1, 0.4, 0.8, 1.6?mg/kg, i.p.) were administered 24?h before testing. Locomotor behaviour (open field test) and motor coordination (acceleratory rotarod) were assessed. Mice were also observed for 10?min for tremor and vacuous chewing movement (VCM). CPZ and Res dose-dependently decreased locomotor behaviour and impaired motor coordination (p?<?0.01). RV also decreased locomotor behaviour (4.0?mg/kg; p?<?0.05) but had minimal effect on motor coordination. VCM was lower in the RV group (0.17?±?0.16/10?min) than the Res (6.8?±?1.36/10?min) and Cpz groups (7.83?±?1.95/10?min): F _(4,25)?=?10.703; p?<?0.01. The frequency of bouts of tremor was also lower in the RV group (1.17?±?0.72/10?min) than the Res (21.2?±?5.63/10?min) and Cpz (7.83?±?1.59/10?min) groups: F _(4,25)?=?11.012; p?<?0.001. The root bark extract of R. vomitoria, therefore, has great potential in the management of psychotic disorders.     

The effects of chlorpromazine on the expression of an acquired passive avoidance response in mice

Mice given one-trial passive avoidance training were examined 24 hours later for retention of the acquired response. Testing was carried out with subjects given either chlorpromazine or saline injections before the test session. Three chlorpromazine doses (0.5, 2.0, and 3.5 mg/kg) were used, and three injection times (10, 90, or 180 min before testing). Chlorpromazine was found to impair the expression of the acquired response, both by depressing its initial elicitation and also by apparently facilitating extinction. A second experiment confirmed that extinction rate was indeed increased. A clear dosage effect was observed but injection time was not important in determining the drug's effect. Further experiments were undertaken to clarify the interpretation of the drug's action; in particular, the possibility that the effects might have been caused by a dissociation of learning between the training and test situations was examined. It is suggested that the elevated extinction rates observed during testing when subjects were given chlorpromazine represents a temporary effect resulting from the reduced stimulus control of behaviour. Permanent effects of pre-test drug administration were noted on the initial expression of the learned response.     

The effects of chlorpromazine on the decay and consolidation of short-term memory traces in mice

Summary F₁ hybrids of two highly inbred strains of mice were trained in a one-trial passive avoidance learning situation. Chlorpromazine, in doses of 0.5, 2.0 and 3.5 mg/kg, was administered at one of four injections times, 10 min before and 0.5, 2 and 10 min after learning. Pre-learning drug administration completely blocked acquisition of a learned avoidance response. Post-learning drug effects were more complex, involving reduced expression of avoidance learning but less rapid extinction of the learned response. The results were related to effects of the drug on short-term memory trace decay and consolidation.     

Variation in the hepatotoxic effects of carbon disulphide between different strains of rat

The hepatotoxic effects of carbon disulphide have been investigated in an outbred (Porton) strain of rat and in 8 inbred strains. Carbon disulphide (1.38 mmoles/kg body weight) was administered intraperitoneally to rats which had been pretreated with phenobarbitone and starved. Livers were taken for analysis 24 h later. A considerable genetic variation in the response of rats to carbon disulphide was observed. The extent of centrilobular hydropic degeneration varied greatly between strains and was accompanied by a high incidence of focal coagulative necrosis in the most susceptible rats. Analysis of variance of the accompanying changes in liver weight and water content and in total liver cytochrome P450 content gave statistical confirmation of a strain effect in the response to carbon disulphide. Highly significant strain x treatment interactions for these parameters were attributable to changes after carbon disulphide treatment rather than variation between phenobarbitone pretreated starved controls. The experiments were repeated in two blocks, 3 months apart. Block effects and interactions were significant in some cases but were quantitatively small and did not obscure a ranking based on histological assessment. AGUS rats were least affected by carbon disulphide whereas PVG and LEW rats showed extensive liver damage. Other strains (WA, Porton, F344, BDIX, WAG) showed a gradation of response between these extremes.     

Ethanol intoxication as function of genotype dependent responses in three inbred mice strains

Three strains of mice, ICR Swiss, DBA/2J and C57B1/6J were compared for initial sensitivity, recovery from intoxication, and acute tolerance development to ethanol. The C57B1/6J mice were found to be less sensitive and to recover more rapidly from the effects of the same dose of ethanol than the other two strains treated. None of the strains tested demonstrated acute tolerance to ethanol when given the same dose 3 hours later.     

Strain differences in the effects of chlorpromazine and chlordiazepoxide upon active and passive avoidance in mice

Summary Four inbred strains of mice were compared on an active and a passive avoidance task in a two-compartment cage. Active mice were trained to cross frequently between compartments to avoid shock; passive mice were shocked for crossing. Yoked controls in both procedures received shocks at the same time as experimentals. Strains learning the active task well did poorly in the passive task; strains poor in active learning were superior on the passive task. The results support the view that strain differences in avoidance learning are more related to variations in strength of a kinetic drive than to strength of fear. Chlordiazepoxide affected crossings similarly in actively and passively trained Ss; chlorpromazine reduced crossings in actively trained and increased crossings in passively trained Ss. This result is consistent with dual motivational systems differentially susceptible to alteration by administration of drugs. Chlordiazepoxide acts primarily upon kinetic drive; chlorpromazine upon fear.This investigation was supported in part by United States Public Health Service Research Grants MH-01775 and MH-11327 from the National Institute of Mental Health.The author acknowledges the technical assistance of Frank Clark and Jane Harris.The principles of laboratory animal care as promulgated by the American Psychological Association were observed in this study.     

Genetic effects on PCP-induced stimulation in recombinant inbred strains of mice

The stimulation of motor activity by phencyclidine was found to differ significantly in BALB/c and C57B1/6By inbred strains of mice. Phencyclidene-induced stimulation was compared for these strains, their reciprocal F1 hybrids, and their recombinant inbred offspring. There were significant differences in responsitivity among the strains, suggesting a genetic influence on the PCP response; however, the strains did not segregate into two distinct groupings, suggesting that this genetic influence was not carried by a single gene. In addition, there was no relationship between the responsitivity of these strains of mice to PCP and their previously-reported responses to amphetamine or scopolamine, which suggests that PCP-induced stimulation is not a simple cholinergic or amphetamine-like response.     

Antidepressant-like effects in various mice strains in the forced swimming test

Rationale. Strain differences in mice have been reported in response to drugs in the mouse forced swimming test (FST), even if few antidepressants were examined. Objectives. The aim of the present study was to investigate the influence of genetic factors, using five antidepressants (imipramine, desipramine, citalopram, paroxetine and bupropion) in the mouse FST, in outbred strains (Swiss, NMRI) and inbred strains (DBA/2, C57BL/6J Rj). Moreover, whole brain levels of dopamine (DA), noradrenaline (NA), serotonin (5-HT) in vehicle treated animals, which were or were not subjected to the FST, were measured by HPLC analysis in an attempt to explain behavioural differences. Methods. For each antidepressant, a dose range (1–16 mg/kg) was tested in the locomotor apparatus and only non-psychostimulant doses were then tested in the FST in order to detect antidepressant-like activity. Results. No baseline differences among Swiss, NMRI, DBA/2 and C57BL/6J Rj strains were observed in our experiments, allowing the comparison of different antidepressants in each strain. Imipramine (16 mg/kg), desipramine, citalopram (4–16 mg/kg) and paroxetine (8 and 16 mg/kg) treatment decreased the immobility time in the Swiss strain and the size of the effect reached more than 20% for each of these antidepressants. C57BL/6J Rj was the only strain sensitive to bupropion (2 and 4 mg/kg). In the NMRI strain, only paroxetine treatment decreased the immobility time (16 mg/kg). Conclusion. Our study showed that drug sensitivity is genotype dependent. FST results have shown that Swiss mice are the most sensitive strain to detect 5-HT and/or NA treatment. The use of DBA/2 inbred mice may be limited, as an absence of antidepressant-like response was observed in the FST. The lack of sensitivity to antidepressant treatment in DBA/2 strains could be due to high DA, NA and 5-HT whole brain concentrations. Electronic Publication     

Comparison of neurobehavioral changes in three inbred strains of mice prenatally exposed to methylmercury

Pregnant mice of three inbred strains (BALB/c, C57BL/6J, C57BL/6Cr) were orally given methylmercury (MMC; 3 x 3 mg/kg body weight) or the equivalent volume of phosphate-buffered saline during days 12-14 of gestation and allowed to deliver. The behaviors of their male offspring were evaluated in an open field and their home cage and in a Morris water maze. In the open field test, the BALB/c and C57BL/6Cr MMC groups exhibited less total locomotor activity than did their respective control groups. However, there was no significant difference observed between the MMC and control C57BL/6J strain. In the BALB/c strain, the MMC group exhibited significantly more central locomotion and significantly less peripheral locomotion than did the control group. These results indicated that the prenatal exposure to MMC caused decreases in open-field activity in the C57BL/6Cr and BALB/c strains, concomitantly with a change in emotional status in BALB/c strain. For spontaneous activity in their home cage, all groups moved more actively in the dark phase than in the light phase except BALB/c MMC group. The BALB/c MMC group moved in the light phase as much as in the dark phase, indicating a disturbance of nocturnal rhythm of spontaneous activity. In the Morris water maze, the C57BL/6Cr and C57BL/6J control groups perform very well over the 5 consecutive days. The prenatal exposure to MMC caused significantly prolonged latency in the C57BL/6Cr and C57BL/6J, but not in BALB/c strain. This result indicated that the prenatal exposure to MMC impaired the performance in the Morris water maze differently among the strains. This study provides a basis for evaluating strain-specific neurobehavioral changes when the widely used three inbred strains of mice are chronically exposed to MMC.     

Dose-dependent effects of heroin on memory in two inbred strains of mice

Heroin was administered to DBA/2 and C57BL/6 mice, trained in the five-choice Yerkes-Thompson-Bryant-Bovet-Nitti apparatus for pattern discrimination, in two sets of experiments. In a first set, pretrial administrations of heroin (0.1, 0.25, or 0.5 mg/kg) improved performance in both strains. In a second set, heroin (0.5 mg/kg) immediately following each training session were followed by performance improvements in both strains, while the performance of C57 mice was improved and that of the DBA mice was impaired by 5 mg/kg of opiate. No effect was evident in this set of experiments when heroin was injected 2 h after each session, suggesting that effects of the pretrial treatments were due to influences of the opiate on the consolidation processes of the strains tested.