TY - JOUR
T1 - Stereotypic behaviors in mice selectively bred for high and low methamphetamine-induced stereotypic chewing
AU - Atkins, A. L.
AU - Helms, M. L.
AU - O'Toole, L. A.
AU - Belknap, J. K.
PY - 2001
Y1 - 2001
N2 - Rationale: At high doses, methamphetamine produces repetitive stereotypic behaviors, and the degree to which this occurs is heritable. Objectives: Mice of a B6D2F2 genetic background were selectively bred for four generations for high (HMA) and low (LMA) numbers of stereotyped chewing episodes measured for 1 min at 33 min post-injection following 10 mg/kg methamphetamine (changed to 7 mg/kg for the high line and 15 mg/kg for the low line in the third selected generation to avoid ceiling and floor effects, respectively). We sought to determine whether stereotypic behaviors other than number of repetitive chewing episodes were altered by the selective breeding process. Methods: HMA and LMA mice of the third and fourth selected generations were tested for chewing stereotypy, for a number of other stereotypic behaviors previously observed in rodents, and for several other non-stereotypic responses to methamphetamine. Testing in the third selected generation was conducted by observing behaviors on videotape following 7 mg/kg methamphetamine. In the fourth selected generation, mice were also tested in automated activity monitors following 10 mg/kg methamphetamine and in climbing chimneys following 16 mg/kg methamphetamine. Dose-response curves with doses of 1, 2, 3.5, 7, 10, and 15 mg/kg methamphetamine were constructed for the most commonly observed behaviors. Results: LMA mice, which exhibited low stereotyped chewing, exhibited high stereotyped circling and climbing, and the reverse was true for these behaviors for HMA mice. For most of the other behaviors measured, there were drug effects but no differences between selected lines. Conclusions: These results suggest that these three stereotyped behaviors, chewing, circling, and climbing, at least partly share the same mechanisms, and therefore are influenced by at least some of the same genes, since animals selectively bred for low methamphetamine-induced stereotyped chewing exhibited high amounts of circling and climbing when given methampetamine. This also suggests that the other stereotypic behaviors that we measured do not occur by the same genetically determined mechanisms as stereotypic chewing.
AB - Rationale: At high doses, methamphetamine produces repetitive stereotypic behaviors, and the degree to which this occurs is heritable. Objectives: Mice of a B6D2F2 genetic background were selectively bred for four generations for high (HMA) and low (LMA) numbers of stereotyped chewing episodes measured for 1 min at 33 min post-injection following 10 mg/kg methamphetamine (changed to 7 mg/kg for the high line and 15 mg/kg for the low line in the third selected generation to avoid ceiling and floor effects, respectively). We sought to determine whether stereotypic behaviors other than number of repetitive chewing episodes were altered by the selective breeding process. Methods: HMA and LMA mice of the third and fourth selected generations were tested for chewing stereotypy, for a number of other stereotypic behaviors previously observed in rodents, and for several other non-stereotypic responses to methamphetamine. Testing in the third selected generation was conducted by observing behaviors on videotape following 7 mg/kg methamphetamine. In the fourth selected generation, mice were also tested in automated activity monitors following 10 mg/kg methamphetamine and in climbing chimneys following 16 mg/kg methamphetamine. Dose-response curves with doses of 1, 2, 3.5, 7, 10, and 15 mg/kg methamphetamine were constructed for the most commonly observed behaviors. Results: LMA mice, which exhibited low stereotyped chewing, exhibited high stereotyped circling and climbing, and the reverse was true for these behaviors for HMA mice. For most of the other behaviors measured, there were drug effects but no differences between selected lines. Conclusions: These results suggest that these three stereotyped behaviors, chewing, circling, and climbing, at least partly share the same mechanisms, and therefore are influenced by at least some of the same genes, since animals selectively bred for low methamphetamine-induced stereotyped chewing exhibited high amounts of circling and climbing when given methampetamine. This also suggests that the other stereotypic behaviors that we measured do not occur by the same genetically determined mechanisms as stereotypic chewing.
KW - B6D2F
KW - Methamphetamine
KW - Selected mouse lines
KW - Stereotypy
UR - http://www.scopus.com/inward/record.url?scp=0034884790&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0034884790&partnerID=8YFLogxK
U2 - 10.1007/s002130100774
DO - 10.1007/s002130100774
M3 - Article
C2 - 11512049
AN - SCOPUS:0034884790
SN - 0033-3158
VL - 157
SP - 96
EP - 104
JO - Psychopharmacology
JF - Psychopharmacology
IS - 1
ER -