Automated Activity Monitoring Research Articles

Behavioural and neurochemical response of α-synuclein A30P transgenic mice to the effects of L-DOPA

Transgenic mice carrying human A30P mutated α-synuclein demonstrate hypolocomotion and dysfunction of the presynaptic machinery of dopamine overflow, induced by reducing capacity of the dopamine storage pool. We suggested that overexpression of α-synuclein may change sensitivity of these mice to L-DOPA. Current study assessed behavioural and neurochemical responses in A30P mice to L-DOPA using automated activity monitoring and voltammetry. We confirmed decreased locomotion and rearing of A30P transgenic mice compared to wild-type controls. L-DOPA (10–200 mg/kg, i.p.) dose-dependently lowered locomotor activity, including stereotypy, in both genotypes, but the effects were larger in A30P mice. The effects of drug on stimulated dopamine overflow were investigated in the nucleus accumbens shell. L-DOPA at the dose of 30 mg/kg did not change peak dopamine overflow induced by 10 Hz stimulation of the medial forebrain bundle in either genotype, but increased it at the higher (20–50 Hz) frequencies of stimulation. At the higher frequencies of stimulation, L-DOPA elevated dopamine overflow significantly more in A30P mice than in the control animals. These data show that A30P transgenic mice are more sensitive to the effects of L-DOPA at both behavioural and neurochemical level.

Collagen‐induced arthritis as a model of hyperalgesia: Functional and cellular analysis of the analgesic actions of tumor necrosis factor blockade

There is a disparity in the animal models used to study pain in rheumatoid arthritis (RA), which tends to be acute in nature, and models used to assess the pathogenesis of RA. The latter models, like human RA, are lymphocyte-driven and polyarthritic. We assessed pain behavior and mechanisms in collagen-induced arthritis (CIA), the model of preclinical arthritis used most commonly in the field of immunology. We then validated the model using anti-tumor necrosis factor (anti-TNF) therapy, which has analgesic effects in models of inflammation as well as in human RA. CIA was induced in DBA/1 mice by immunization with type II collagen at the base of the tail. Swelling and mechanical and thermal hyperalgesia were assessed before and for 28 days after the onset of arthritis. Spontaneous behavior was assessed using an automated activity monitor. Glial activity was assessed by glial fibrillary acidic protein expression, and nerve damage was evaluated by activating transcription factor 3 expression. The actions of anti-TNF therapy on nociception were then evaluated. Arthritis resulted in a decrease in the threshold for thermal and mechanical stimuli, beginning on the day of onset. Decreased spontaneous activity was also observed. A significant increase in the number of hyperplasic spinal cord astrocytes was observed beginning 10 days after the onset of arthritis. Anti-TNF therapy was profoundly analgesic, with an efficacy similar to that of cyclooxygenase 2 inhibition, and reduced astrocyte activity in CIA. This study shows that the CIA model is suitable for testing not only antiinflammatory but also analgesic drugs for potential use in RA, and highlights the importance of using appropriate disease models to assess relevant pain pathways.

Lobeline augments and inhibits cocaine-induced hyperactivity in rats

Lobeline has high affinity for nicotinic receptors and alters presynaptic dopamine storage and release in brain. Moreover, lobeline decreases the reinforcing and locomotor-activating properties of methamphetamine, suggesting that lobeline may be a pharmacotherapy for psychostimulant abuse. This study determined if lobeline alters cocaine-induced hyperactivity and if lobeline alters the induction and/or expression of sensitization to cocaine. On Days 1–12, male rats were administered lobeline (0.3 or 1.0 mg/kg) or saline, placed in an automated activity monitor for 20 min, administered cocaine (10, 20 or 30 mg/kg) or saline and returned to the monitor for 60 min. On Day 13, the effect of lobeline on the induction and expression of sensitization to cocaine was determined. Lobeline did not alter the effect of cocaine after acute injection. However, 1.0 mg/kg lobeline attenuated cocaine (10 and 20 mg/kg)-induced hyperactivity after repeated administration and prevented the development of sensitization to these cocaine doses. Interestingly, 0.3 mg/kg lobeline augmented cocaine (10 mg/kg)-induced hyperactivity after repeated administration. Lobeline did not alter the effect of 30 mg/kg cocaine. The present results indicate a complex interaction of lobeline with cocaine and support other research indicating a role for nicotinic receptors in the development of sensitization to psychostimulants.

Modulation of fra‐2 and σ receptor gene and protein expression is correlated with the ability of a σ receptor antagonist to attenuate cocaine‐induced sensitization

Sigma (σ) receptors have recently been implicated in the actions of cocaine, and antagonists of these receptors prevent many acute and subchronic cocaine effects, including sensitization. However, the underling mechanisms are still unclear. An earlier study in our lab showed that acute administration cocaine can alter fra-2 and σ receptor gene and protein expression. Based on this result, we hypothesized that cocaine-induced changes in fra-2 and σ receptor gene and protein expression may contribute to the development of behavioral sensitization. Mice were randomly divided into four treatment groups (Saline+Saline, Saline+Cocaine, BD1063+Cocaine, BD1063+Saline), then injected once a day for five days with a locomotor stimulatory dose of cocaine (Days 1–5), followed by a 10 day drug-free period, and subsequently challenged with cocaine (Day 15). Locomotor activity was monitored on each day using an automated activity monitoring system. On Days 1, 3, 5 or 15, the brains of the animals were collected for subsequent measurements of fra-2 and σ receptor mRNA and protein levels. The results showed that the σ receptor antagonist BD1063 attenuates cocaine-induced changes in behavior, gene and protein expression. Together, the data suggest that the ability of the σ receptor antagonist to modulate fra-2 and σ receptor gene and protein expression contributes to its ability to attenuate cocaine-induced sensitization.

Chronic exposure to MDMA (Ecstasy) elicits behavioral sensitization in rats but fails to induce cross-sensitization to other psychostimulants

BackgroundThe recreational use of 3,4-methylenedioxymethamphetamine (MDMA, ecstasy) among adolescents and young adults has become increasingly prevalent in recent years. While evidence suggests that the long-term consequences of MDMA use include neurodegeneration to serotonergic and, possibly, dopaminergic pathways, little is known about susceptibility, such as behavioral sensitization, to MDMA.MethodsThe objectives of this study were to examine the dose-response characteristics of acute and chronic MDMA administration in rats and to determine whether MDMA elicits behavioral sensitization and whether it cross-sensitizes with amphetamine and methylphenidate. Adult male Sprague-Dawley rats were randomly divided into three MDMA dosage groups (2.5 mg/kg, 5.0 mg/kg, and 10.0 mg/kg) and a saline control group (N = 9/group). All three MDMA groups were treated for six consecutive days, followed by a 5-day washout, and subsequently re-challenged with their respective doses of MDMA (day 13). Rats were then given an additional 25-day washout period, and re-challenged (day 38) with similar MDMA doses as before followed by either 0.6 mg/kg amphetamine or 2.5 mg/kg methylphenidate on the next day (day 39). Open-field locomotor activity was recorded using a computerized automated activity monitoring system.ResultsAcute injection of 2.5 mg/kg MDMA showed no significant difference in locomotor activity from rats given saline (control group), while animals receiving acute 5.0 mg/kg or 10.0 mg/kg MDMA showed significant increases in locomotor activity. Rats treated chronically with 5.0 mg/kg and 10.0 mg/kg MDMA doses exhibited an augmented response, i.e., behavioral sensitization, on experimental day 13 in at least one locomotor index. On experimental day 38, all three MDMA groups demonstrated sensitization to MDMA in at least one locomotor index. Amphetamine and methylphenidate administration to MDMA-sensitized animals did not elicit any significant change in locomotor activity compared to control animals.ConclusionMDMA sensitized to its own locomotor activating effects but did not elicit any cross-sensitization with amphetamine or methylphenidate.

Chronic pretreatment with methylphenidate induces cross-sensitization with amphetamine

Consequence of the long-term use of psychostimulants as treatment for attention deficit/hyperactivity disorder (ADHD) is unknown, particularly whether treatment with psychostimulants at an early age increases an individual's potential for cross-sensitization to other stimulants exposed at a later age. Cross-sensitization occurs when pretreatment with one stimulant leads to greater sensitivity to another stimulant. The aims of this study were to investigate whether chronic treatment with methylphenidate (MPD; Ritalin) in both juvenile and adult rats induced cross-sensitization to amphetamine at a later time and whether this cross-sensitization to amphetamine was age-dependent. Male Sprague-Dawley rats were randomly divided into four treatment groups: (1) group treated intraperitoneally (i.p.) with saline as juveniles and adults, (2) group treated with 0.6 mg/kg amphetamine, i.p., as juveniles and adults, (3) group treated with 2.5 mg/kg MPD, i.p., as juveniles and adults, and (4) group treated with saline, i.p., as juveniles and 2.5 mg/kg MPD, i.p., as adults. All of the animals received an amphetamine (0.6 mg/kg, i.p.) challenge on the last experimental day. We examined the effects of chronic MPD treatment in juvenile and adult rats on their locomotor response to an acute amphetamine exposure. Three different locomotor indices were studied using an automated activity monitoring system. Changes in the locomotor responses to amphetamine of these animals were compared to those of control rats that were pretreated with saline as juveniles and as adults. It was found that prior chronic treatment with MPD produced cross-sensitization to the locomotor response to amphetamine as observed in the horizontal activity and total distance traveled. It also appears that this cross-sensitization to amphetamine may not be dependent on the age of the subjects, i.e., whether subjects were juvenile or adult rats when they received drugs, but rather it depended on the behavioral index examined.

Strain differences in the behavioral responses of male rats to chronically administered methylphenidate

Genetic variability in the behavioral responses of experimental subjects to psychostimulants such as amphetamine and cocaine have been reported. However, genetic differences in the locomotor responses of rat strains to methylphenidate (MPD), a commonly used psychostimulant in the treatment of attention deficit/hyperactivity disorder, have not been extensively investigated. Research using genetically defined rodent strains can enhance our understanding of the role genetic factors play in drug-related behaviors and the development of animal models for drug-sensitive diseases or behaviors. The objective of the present study was to investigate strain differences in the locomotor responses to MPD among three rat strains: Sprague–Dawley (SD), Wistar–Kyoto (WKY), and spontaneously hypertensive rats (SHR). Eight-week-old adult, male SD, WKY, and SHR were given a regimen of daily MPD administration (0.6, 2.5, or 10 mg/kg, i.p.) for 6 consecutive days followed by 3 days of washout and a day of MPD re-challenge with similar dosages as previously used. An automated activity monitoring system recorded their horizontal activity, total distance traveled, rearing, stereotypic movements, and number of discrete movements. Repeated administration of 0.6 mg/kg MPD produced no significant effect on locomotor activity compared with saline in all three strains. However, there were strain differences in the locomotor activity of SD, SHR, and WKY rats to repeated 2.5- and 10-mg/kg MPD treatment. Repeated administration of 2.5 mg/kg MPD elicited locomotor sensitization in SD and WKY rats but not in SHR. Repeated administration of 10 mg/kg MPD induced locomotor tolerance in SD and WKY rats, while SHR had variable locomotor responses to this MPD dose. In conclusion, rat strains play a significant role in the response to acute and chronic administration of MPD.

Central effects of urotensin-II following ICV administration in rats

Urotensin-II (U-II) has recently been identified as an agonist for the G-protein-coupled receptor, GPR14. Detection of both U-II and GPR14 mRNA in the brain and spinal cord is consistent with a role for U-II in the CNS. However, the effects of central administration of U-II in rodents have not been reported previously. To determine the localisation of GPR14 mRNA in rat tissues and to investigate the behavioural and endocrine effects of human U-II (hU-II) following intracerebroventricular (ICV) administration in rats. Experiments were carried out in male Sprague-Dawley rats. Expression of GPR14 mRNA in rat brain was determined by semi-quantitative RT-PCR. Effects of hU-II on general behaviours were assessed by an observer and the motor activity response was measured by an automated activity monitor. Plasma hormones and [DOPAC + HVA]/[DA] and [5-HIAA]/[5-HT] ratios in five brain areas were measured 20 min post-hU-II (ICV). GPR14 mRNA expression was found in whole brain tissue and in all CNS regions tested. GPR14 mRNA expression was also detected in the periphery; highest levels were found in the heart. Following ICV administration, hU-II (3-10 micrograms ICV) increased rearing and grooming, and increased motor activity in a familiar environment. Further, hU-II increased plasma prolactin and TSH but did not affect levels of corticosterone. hU-II had no effects on dopamine or 5-HT levels or their metabolites in the frontal cortex, hippocampus, hypothalamus, striatum and nucleus accumbens. These data provide further insight into the distribution of GPR14 mRNA within the CNS and show for the first time that hU-II causes marked behavioural and endocrine effects.

Effects of centrally administered orexin-B and orexin-A: a role for orexin-1 receptors in orexin-B-induced hyperactivity

Orexin-A and orexin-B are hypothalamic neuropeptides derived from a 130-amino acid precursor, prepro-orexin, and are potent agonists at both the orexin-1 (OX1) and orexin-2 (OX2) receptors. Orexin-A has been ascribed a number of in vivo functions in the rat after intracerebroventricular (ICV) administration, including hyperphagia, neuroendocrine modulation and a role in the regulation of sleep-wake function. The in vivo role of orexin-B is not as clear. To investigate the behavioural, endocrine and neurochemical effects of orexin-B in in-vivo tests. In a number of experiments, these effects were compared with those of orexin-A. Experiments were carried out in male, Sprague-Dawley rats with a guide cannula directed towards the lateral ventricle. The effects of orexin-B (ICV) upon grooming behaviour were compared with those of orexin-A. The effects of orexin-B upon the motor activity response to both novel and familiar environments were assessed in an automated activity monitor. Orexin-B was tested upon startle reactivity and body temperature. Further, plasma hormones and [DOPAC+ HVA]/[DA] and [5-HIAA]/[5-HT] ratios in six brain areas were measured 40 min post-orexin-B or orexin-A. The clearest behavioural response to orexin-B was increased motor activity in both novel and familiar environments. Orexin-B-induced hyperactivity was blocked by an OX1 receptor antagonist, SB-334867-A, implicating OX1 receptors in this behavioural response. In common with orexin-A, orexin-B reduced plasma prolactin and failed to influence startle reactivity. However, in contrast with orexin-A, orexin-B increased head grooming but failed to cause a robust whole body grooming response or increase plasma corticosterone levels. Further, orexin-B, but not orexin-A, increased plasma TSH and increased hypothalamic and striatal [5-HIAA]/[5-HT] ratios. The present study has demonstrated a number of behavioural, neuroendocrine and neurochemical effects of orexin-B that distinguish it from orexin-A. Further, we have demonstrated a role for OX1 receptors in the actions of orexin-B upon motor activity.

Open field is more sensitive than automated activity monitor in documenting ouabain-induced hyperlocomotion in the development of an animal model for bipolar illness

1. 1. Intracerebroventricular (ICV) administration of ouabain to rats induces motor hyper- and hypoactivity that have been hypothesized to model the mania and depression of bipolar illness, respectively. 2. 2. The extent of ouabain-induced change in activity may vary according to the test environment. 3. 3. To determine the degree of differential response to ICV ouabain in the open field and automated activity monitors, the authors examined a large number of animals (n = 40) in both environments. 4. 4. ICV ouabain produced a four-fold increase in open field activity versus ICV artificial cerebrospinal fluid (aCSF) (mean ± SD: 258.7 ± 316.61 vs. 84.8 ± 86.16 squares traversed) (t = 2.648, P = 0.011). but did not alter horizontal activity in automated activity monitors (8193.5 ± 4902.52 vs. 7088.47 ± 3046.85 beam interruptions) (t = 0.847, P = 0.4). This increase in activity persisted for at least one week (161.0 ± 186.35 for ICV ouabain vs. 46.1 ± 47.46 for ICV aCSF. P = 0.065). 5. 5. Open field is superior to automated activity monitors in capturing ouabain- induced hyperlocomotion response.

Food availability and the nocturnal vs. diurnal foraging trade‐off in juvenile salmon

1.Much attention has been devoted to explaining the spatial distribution of foraging animals, but rather little to their temporal distribution (i.e. whether they are diurnal, nocturnal or crepuscular). Many animals face predictable diel cycles of food availability or predation risk, and so the approach of measuring the relative ratio of mortality risk to food gained (the ‘minimize μ/f’ rule) can be applied equally as well to different time periods of the day as to alternative food patches or habitats.2.This method is used here to investigate the diel activity patterns of juvenile Atlantic salmon, which have previously been shown to become increasingly biased towards nocturnal activity in winter, hiding for much of the day in streambed refuges. Calculations based on published data show that nocturnal foraging in winter is far safer per unit of food obtained than is diurnal, despite greatly reduced food capture efficiency at night‐time light levels.3.Using an automated activity monitoring system based on passive integrated transponder (PIT) tags, this study shows that winter diel activity patterns in salmon are dependent on food availability. A change in food density led to a parallel change in time spent in the refuge, but (as predicted by the μ/frule) the effect was greatest at the time of day with the least favourable ratio of predation cost to feeding benefit. Thus an experimental increase in food availability led to a 16% reduction in time spent in nocturnal foraging but a 98% reduction in time spent foraging by day, with fish spending only 0·6% of the daylight hours out of the refuge at the highest food density.4.However, brief daytime foraging bouts had a major impact on growth rates (presumably because feeding efficiency was much greater in daylight), especially when food was scarce. Daytime feeding was thus profitable in terms of rapid food acquisition but normally suboptimal in terms of risk of predation.5.Daily activity patterns are therefore suggested to be the result of a complex trade‐off between growth and survival, which takes account of diel fluctuations in food availability, food capture efficiency and predation risk; individual variation in the extent of diurnal feeding in salmon may result from state‐dependent differences in the benefits of rapid feeding and growth.

Effects of Repeated Exposure to Fox Odor on Locomotor Activity Levels and Spatial Movement Patterns in Breeding Male and Female Meadow Voles ( Microtus pennsylvanicus )

Following five days of baseline activity recording, voles were exposed to fox odor for 3 min each day for five days. Immediately following each daily exposure, locomotor activity levels and spatial movement patterns were assessed using an automated activity monitoring system (Digiscan system). Males displayed a significant reduction in levels of various measures of locomotor activity following exposure to fox odor on each exposure day relative to baseline levels. Males preferred the corner of the testing box significantly more on the second day of fox odor exposure relative to baseline. Although females showed only a brief reduction in the number of movements made on the first day of odor exposure, this response lasted significantly longer on each of the subsequent odor exposure days. The reliability of the reductions in activity levels displayed across days by breeding male voles supports the hypothesis that this response is adaptive. Furthermore, the results suggest that, although female voles do not generally display this behavioral response, it can be elicited in females when the predation threat is repeated in consistent context.

Ethanol Modulates Cocaine-Induced Behavioral Change in Inbred Mice

We recently conducted a study of the behavioral effects of combined cocaine and ethanol in genetically defined mice. Male and female C57BL/6 (B6) and DBA/2 (D2) were tested in an automated activity monitor on 2 consecutive days. On day 1, all animals received an IP injection of sterile saline and were placed into the activity monitor for 30 min. Behaviors measured were total distance traveled, stereotypy, nosepokes, and wall-seeking. On day 2, all animals were tested again for 15 min following injection of one of the following: saline, 10% v/v ethanol at 2.0 g kg 21 or 2.0 g kg 21 ethanol plus 5, 15, or 30 mg kg 21 cocaine. Cocaine alone at the same doses was injected into separate groups of animals. For the B6 strain, the overall effect of ethanol was to reduce cocaine-induced locomotor stimulation; no consistent effect of ethanol on cocaine-induced locomotion was observed in D2 mice. Cocaine-induced inhibition of nosepokes in both strains and sexes was partially reversed by ethanol. Ethanol also partially reversed cocaine-elevated stereotypy in both strains and both sexes. In B6 mice, cocaine-increased wall seeking tended to be reversed by coadministration of ethanol, whereas no consistent pattern was observed in the D2s. Results from this study suggest that the several measures affected by cocaine (locomotor activity, stereotypy, exploration, thigmotaxis) were, in turn, differentially affected by concurrent treatment with ethanol. Furthermore, our results point to genetic-based differences in ethanol’s effects on cocaine-related behaviors. We address the implications for combined ethanol and cocaine use in humans.

Exposure to Predator Odor Reduces Locomotor Activity Levels in Adult Male Rats: Lack of Effect of Hippocampal Lesion

The hippocampus has been implicated in mediating responses to predators. Involvement of the hippocampus was tested in the present study in which a multivariate analysis of the locomotor activity of intact and hippocampectomized (destruction of dentate and CA1 cells) laboratory rats, Rattus norvegicus, was conducted following exposure to a predator odor. Levels of various activity variables were monitored in an automated activity monitoring system following a brief 3-min exposure to 2-propylthietane (weasel odor), caproic acid (goat odor), toluene (organic solvent), and a no-odor condition in hippocampal-lesioned (using colchicine) and sham-operated control male rats. Rats of both groups displayed reduced levels of total distance, movement time, vertical activity, and number of movements following exposure to weasel odor and toluene in comparison to the no-odor condition. Exposure to goal odor resulted only in reduced levels of vertical activity and number of movements. There were no differences in activity levels between hippocampal-lesioned and sham-operated rats during baseline activity recording or following exposure to any of the odors. However, hippocampal-lesioned rats spent less lime in the center of the activity boxes than sham-operated control rats across all conditions. This study demonstrates that laboratory rats show marked changes in locomotion in response to the odor of a predator and suggests that an intact hippocampus is not essential for mediating these responses.

Anxiety- and activity-related effects of diazepam and chlordiazepoxide in the rat light/dark and dark/light tests

We have investigated, through factor analysis, anxiety- and activity-related variables in rats placed in the light/dark box. Thus, vehicle-, diazepam (DZ)-, and chlordiazepoxide (CDP)-treated rats were submitted 30 min later to 5-min light/dark or dark/light tests (initial placements in light or dark, respectively). Following this test, the animals were tested for 5 min in an automated activity monitor. Doses of DZ (0.75–3.0 mg/kg) and CDP (2.5–10.0 mg/kg) were based on preliminary evidence for 1.5 mg/kg of DZ and 5 mg/kg of CDP being anxiolytic in the elevated plus-maze. In the light/dark test, DZ increased the number of visits to and duration in the light compartment, and locomotor activity in the dark compartment; moreover, DZ decreased the latency to enter the light compartment. These effects were, however, significant for the highest dose only. Although CDP yielded similar behavioural effects, only the highest dose had a significant effect, namely, on latency to enter the light side. Conversely, none of the other variables were benzodiazepine-sensitive. Locomotion in the activity cages was decreased by DZ and CDP, an effect significant for the highest doses of benzodiazepines (dark/light test condition only). In both tests, factor analyses revealed an anxiety-related factor (to which all variables related to the visits in the light and part of the locomotion in the dark contributed), and an activity-related factor (upon which the latency to enter the dark and part of the locomotion in the dark loaded) in the light/dark test only. It is suggested that although the light/dark and dark/light tests capture an approach/avoidance dimension, DZ and CDP are more effective in the former test. Compared to the light/dark test, however, the plus-maze may be more sensitive to the anxiolytic effects of DZ and CDP.

Behavioral responses to low doses of cocaine are affected by genetics and experimental history

We recently conducted a set of two experiments to investigate the possible co-operation between genetics and exposure to novelty on the putative locomotor inhibiting effects of low doses of cocaine in male and female C57BL/6 and DBA/2 mice. Experiment one examined the effects of three low doses of cocaine (0.1, 0.5, and 1.0 mg/kg) on locomotion, exploration, stereotypy and wall-seeking in an automated activity monitor. Testing occurred on two consecutive days, with subjects receiving an IP injection of saline on day one, and one dose of cocaine on day 2 (S-C). Immediately following injection, subjects were placed into automated activity monitors, where four behaviors were recorded; total distance, nosepokes, stereotypy and margin time. Using this S-C injection regimen, we found significant decreases in measures of total distance and stereotypy when compared to saline in both male and female C57 mice. Experiment two was designed to determine if the observed decrease in locomotor activity was the result of low-dose cocaine or pre-exposure to the test procedure and apparatus. All conditions and procedures were identical to those in experiment one, with the exception of the injection regimen. In this experiment, we injected all subjects IP with 0.1 mg/kg cocaine on day one, followed by saline on day two (C-S). Additionally, a group of subjects receiving saline on both days (S-S) served as the control. In contrast to experiment one results, cocaine produced locomotor activation. Furthermore, significant sex and strain differences were found in both experiments. The results of our experiments suggest that the behavioral effects of low doses of cocaine are markedly influenced by both the genetic constitution of the experimental animal and by familiarity with the test apparatus.

Validation of an automated activity monitor system using d-amphetamine and phenobarbital : HENCK, J.W., D. TRAXLER FRAHM, R. PELTON, AND J.A. ANDERSON, Parke-Davis Pharmaceutical Research, Warner-Lambert Co., Ann Arbor, Michigan

Validation of an automated activity monitor system using d-amphetamine and phenobarbital : HENCK, J.W., D. TRAXLER FRAHM, R. PELTON, AND J.A. ANDERSON, Parke-Davis Pharmaceutical Research, Warner-Lambert Co., Ann Arbor, Michigan

Alterations in activity following alcohol administration during the third trimester equivalent in P and NP rats.

There is considerable variation in the consequences of alcohol abuse during pregnancy on infant outcome. Although it is clear that a number of factors contribute to this variability, one hypothesis that has received recent attention is the role of genetic differences in response to alcohol. This study examined activity levels in the alcohol-preferring (P) and alcohol-nonpreferring (NP) rats following neonatal alcohol exposure. Although these lines were selectively bred for differences in voluntary alcohol consumption, they also differ in their sensitivity and tolerance to alcohol. The P and NP offspring were artificially reared and administered ethanol (either 6 or 4 g/kg/day) from postnatal day 4 (PN 4) until PN 10 via intragastric cannula. An artificially reared isocaloric maltose group and a normally reared control group were also included. From PN 18 to PN 21, subjects were tested daily for 30 min in an automated activity monitor. Exposure to either the 4 or 6 g/kg dose of ethanol resulted in overactivity in P rats. However, only the 6 g/kg dose group displayed overactivity among the NP offspring. Furthermore, the level of overactivity displayed by the alcohol-exposed P rats was significantly greater than that displayed by the alcohol-exposed NP rats. These data suggest that genetic differences in response to alcohol may be a predictor for the behavioral teratogenic effects of alcohol.

Pharmacogenetics of cocaine: I. Locomotor activity and self-selection

We investigated the effects of cocaine on multiple activity measures and cocaine self-selection in C57BL/6Ibg and DBA/2Ibg mice. Male mice were tested in an automated activity monitor at three doses of cocaine, 5, 15 and 30 mg kg-1. Activity measures included locomotion, rearings, stereotyped movements and wall-seeking. Testing was conducted on 2 days with saline injection, i.p. on day one and cocaine i.p. injected on day two. We also tested other mice of both strains for cocaine ingestion in a two-choice test, pairing tap water with 40 mg% cocaine HCl in tap water. Two separate groups of mice received 15 or 30 mg kg-1 of cocaine i.p., killed at 5 min and brain cocaine levels were determined by HPLC. Cocaine produced dose-related increases in locomotion in both strains, with a delay in initial activation noticed at 30 mg kg-1 in C57s but not in DBAs. In DBAs, cocaine suppressed rearings and increased stereotyped movements while having no consistent effect on either behaviour in C57s. At all doses, cocaine produced moderate increases in proximity to the wall in DBAs and 30 mg kg-1 produced pronounced wall-seeking in C57s. At 15 and 30 mg kg-1 DBAs tended to have higher levels of cocaine in whole brain than did C57s. Finally, C57s consumed significantly more cocaine than did the DBAs.

Equine reproduction (1993)

The objectives of this observational study were to assess the ability of automated activity monitoring (AAM) to detect estrus for first insemination, the accuracy of detection, and the optimum interval from the estrus alert from the AAM system to insemination. Four commercial farms using 1 of 2 commercial AAM systems were studied over 1 yr. Cows were inseminated between 55 and 80 d in milk (DIM) based on AAM only, then by a combination of AAM and timed artificial insemination (AI). Blood progesterone was measured in 1,014 cows at wk 5, 7, and 9 postpartum; purulent vaginal discharge (PVD) was assessed at wk 5; and lameness and BCS at wk 7. Overall, AAM detected 83% of cows in estrus by 80 DIM. Cows that had 3 serum progesterone <1 ng/mL, had PVD, or were both lame and had BCS ≤2.5 has lesser odds of being detected in estrus by 80 DIM (62, 68, and 53%, respectively). Blood samples were collected on the day of 445 AI based on AAM and 323 timed AI. The proportion of cows not in estrus (progesterone >1 ng/mL) on the day of AI was similar between AAM (4 ± 1.8%) and timed AI (3 ± 1.2%). Managers elected, based on subjective criteria, not to inseminate 17% of cows for which an AAM estrus alert was issued, of which 43% were not in estrus. Activity data were extracted from AAM software for 1,399 AI. Onset of estrus was calculated using the same or similar data processing criteria as the AAM system. Producers recorded the time of AI. The interval from onset of estrus to AI was categorized as 0 to 8, 8 to 16, or 16 to 24 h. We found no effect of AAM system on the probability of pregnancy per AI, but noted an interaction of interval with parity. For multiparous cows, the probability of pregnancy per AI was 31%, which did not differ with the interval to AI. For primiparous cows, the odds of pregnancy were greater if AI occurred 0 to 8 h (49%) than 8 to 16 (36%) or 16 to 24 h (31%) after the estrus alert from the AAM. Automated activity monitoring can detect estrus for first AI in just over the length of 1 estrous cycle for over 80% of cows, but the remainder would likely require intervention for timely insemination. For multiparous cows, performing AI based on AAM once per day would not affect pregnancy per AI, but for primiparous cows AI within 8 h of the onset of estrus may be advantageous.