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Strain differences in radial arm maze performance of rats
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Book ofAbstmcts - EUROTOX ‘94
Strain Differences in Radial Arm Maze Performance of Rats G.Osteroaard. institute of Tbxicolo~. National Food Agency of Denmark, Seborg, Denmark Rats of three different strains,one outbred and two inbred, (WisSr. Mol: WIST; Long-Evans,LE/Mol. Sprague-Dawlel, SPRD/Mol; n = 10 in each group) were tested in a delayed-non-match-to-sample radial maze training procedure. Throughout the entire test period, the rats were fed a restricted amount of food. Testing was initiated with one week’s adaptation where rats were placed daily in the radial maze for five minutes each. This was followed by four weeks of testing consisting of one daily training session per rat with all eight arms open and baited (classical procedure). During this period, a stable performance was established. The remaining two weeks’ training consisted of two daily sessions: In the tirst. four arms were shut, and the remaining four arms were baited. The rat was allowed to collect the bait, after which it was removed from the maze to the home cage for one hour. In the second session all arms were open and bait was placed in those arms only that had previously been shut (delayed non-match-tosample procedure). Analysis of various aspects of performance in the maze showed comparable learning ability of all three strains; however, certain differences existed. The use of inbred rather than outbred strains could not be demonstrated to reduce individualvariability. Key word..: cognitive function; working memory; strain-specific behaviour
Developmental and Behavioral Effects of Prenatal Amitraz Exposure in Rats .I. Palermo-Neto. J.C. Flbrio. M. Sakate. School of Vet. Medicine. Universityof 80 Paula, S.P, Brasil The effects of prenatal amitraz exposure on physical and behavioral parameters of rats were studied. Pregnant rats were orally gavaged with amitraz (20 mg/kg) or with distilled water (1 .O ml/kg) on days 1,4,7,10, 13, 16 and 19 of pregnancy. After birth the cross-fostering procedure was performed thus generating the following groups: con?roi pups nursed by controls dams (CC), control pups nursed by treated dams (CE). treated pups nursed by treated dams (EE) and treated pups nursed by control dams (EC). Results show that compared to pups of group CC, groups prenatally exposed to amitraz (EC and EE) showed decreased age of vaginal opening. Group EE also showed early fur development and a delay in incisor eruption compared to group CC. The ages of pina detachment, eye and ear opening, testes descent, and reflex development (surface righting and startle) were not affected byamitraz exposure. Offspring of group CE also showed earlier fur development. Rats ot group EE had higher locomotor activity and rearing frequency and shorter immobility time compared to rats of group CC when observed i.,an Dpen-field 30 days after birth but not 60 and 9” days. No significantdifferences were found in open-field behaviors among the CC. CE and EC groups. The present findings indicate that prenatal exposure to amitraz caused transient developmental and behavioral changes in the exposed rat offspring. Key words: amitraz; behavioralteratology; usvelopmental neurotoxilogy
The Timing of Toxtcity Studies in Relation to Clinical Investigation C. Parkinson, K. Thomas, N. McAuslane. C.E. Lumley Centre for Medicines Research, Woodmansterne Road, Carshalton,Surrey SM5 40s. UK The recommendations for the extent of nonclinical testing to support the various stages of clinical development of phamlaceuticals frequently differ between the regions of Europe, Japan and the USA. To contribute to the discussions taking place on this topic, including those in the ICH process, and to provide an international overview of current thinking and practice, the CMR is conducting a questionnaire-based survey. Sixty seven international pharmaceutical companies or their subsidiaries were contacted to obtain information on the timing of toxicity studies, including current practice and a proposed ideal toxicity testing strategy to support (i) the first administration in humans, (ii) repeated dosing in clinical trials and (iii) the inclusion of women in clinical trials. Preliminary results show that the main difference in toxicity testing before the first administration to man between regions is that Japanese companies conduct male and female fertility studies at this stage. Three European companies also conduct reproductive toxicity studies before Phase I, however they indicated they would not do so in an ideal situation. There was a variety of combinations of repeated dose toxicity studies carried out to support the different stages of clinical development. About one third of the respondents indicated that a carcinogenicity study was completed prior to initiating Phase Ill trials. The ideal repeated dose toxicology strategy for most companies differed from the current approach. implyingthat the regula?oryguidelines on repeated dose toxicity studies present more problems, in terms of their scientific rationale,than other areas of toxicology It is hoped that this survey will provide an insight into some of the most recent developments in international pre-clinicalstrategic thinking.
Book ofAbstmcts - EUROTOX ‘94
Strain Differences in Radial Arm Maze Performance of Rats G.Osteroaard. institute of Tbxicolo~. National Food Agency of Denmark, Seborg, Denmark Rats of three different strains,one outbred and two inbred, (WisSr. Mol: WIST; Long-Evans,LE/Mol. Sprague-Dawlel, SPRD/Mol; n = 10 in each group) were tested in a delayed-non-match-to-sample radial maze training procedure. Throughout the entire test period, the rats were fed a restricted amount of food. Testing was initiated with one week’s adaptation where rats were placed daily in the radial maze for five minutes each. This was followed by four weeks of testing consisting of one daily training session per rat with all eight arms open and baited (classical procedure). During this period, a stable performance was established. The remaining two weeks’ training consisted of two daily sessions: In the tirst. four arms were shut, and the remaining four arms were baited. The rat was allowed to collect the bait, after which it was removed from the maze to the home cage for one hour. In the second session all arms were open and bait was placed in those arms only that had previously been shut (delayed non-match-tosample procedure). Analysis of various aspects of performance in the maze showed comparable learning ability of all three strains; however, certain differences existed. The use of inbred rather than outbred strains could not be demonstrated to reduce individualvariability. Key word..: cognitive function; working memory; strain-specific behaviour
Developmental and Behavioral Effects of Prenatal Amitraz Exposure in Rats .I. Palermo-Neto. J.C. Flbrio. M. Sakate. School of Vet. Medicine. Universityof 80 Paula, S.P, Brasil The effects of prenatal amitraz exposure on physical and behavioral parameters of rats were studied. Pregnant rats were orally gavaged with amitraz (20 mg/kg) or with distilled water (1 .O ml/kg) on days 1,4,7,10, 13, 16 and 19 of pregnancy. After birth the cross-fostering procedure was performed thus generating the following groups: con?roi pups nursed by controls dams (CC), control pups nursed by treated dams (CE). treated pups nursed by treated dams (EE) and treated pups nursed by control dams (EC). Results show that compared to pups of group CC, groups prenatally exposed to amitraz (EC and EE) showed decreased age of vaginal opening. Group EE also showed early fur development and a delay in incisor eruption compared to group CC. The ages of pina detachment, eye and ear opening, testes descent, and reflex development (surface righting and startle) were not affected byamitraz exposure. Offspring of group CE also showed earlier fur development. Rats ot group EE had higher locomotor activity and rearing frequency and shorter immobility time compared to rats of group CC when observed i.,an Dpen-field 30 days after birth but not 60 and 9” days. No significantdifferences were found in open-field behaviors among the CC. CE and EC groups. The present findings indicate that prenatal exposure to amitraz caused transient developmental and behavioral changes in the exposed rat offspring. Key words: amitraz; behavioralteratology; usvelopmental neurotoxilogy
The Timing of Toxtcity Studies in Relation to Clinical Investigation C. Parkinson, K. Thomas, N. McAuslane. C.E. Lumley Centre for Medicines Research, Woodmansterne Road, Carshalton,Surrey SM5 40s. UK The recommendations for the extent of nonclinical testing to support the various stages of clinical development of phamlaceuticals frequently differ between the regions of Europe, Japan and the USA. To contribute to the discussions taking place on this topic, including those in the ICH process, and to provide an international overview of current thinking and practice, the CMR is conducting a questionnaire-based survey. Sixty seven international pharmaceutical companies or their subsidiaries were contacted to obtain information on the timing of toxicity studies, including current practice and a proposed ideal toxicity testing strategy to support (i) the first administration in humans, (ii) repeated dosing in clinical trials and (iii) the inclusion of women in clinical trials. Preliminary results show that the main difference in toxicity testing before the first administration to man between regions is that Japanese companies conduct male and female fertility studies at this stage. Three European companies also conduct reproductive toxicity studies before Phase I, however they indicated they would not do so in an ideal situation. There was a variety of combinations of repeated dose toxicity studies carried out to support the different stages of clinical development. About one third of the respondents indicated that a carcinogenicity study was completed prior to initiating Phase Ill trials. The ideal repeated dose toxicology strategy for most companies differed from the current approach. implyingthat the regula?oryguidelines on repeated dose toxicity studies present more problems, in terms of their scientific rationale,than other areas of toxicology It is hoped that this survey will provide an insight into some of the most recent developments in international pre-clinicalstrategic thinking.