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Stereotypic behaviors in mice selectively bred for high and low methamphetamine-induced stereotypic chewing
A L Atkins1, M L Helms, L A O'Toole
1Department of Behavioral Neuroscience, Oregon Health & Sciences University, 3710 SW US Veterans Hospital Road, R & D5, Portland, OR 97201, USA. atkinsa@ohsu.edu
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 methamphetamine. This also suggests that the other stereotypic behaviors that we measured do not occur by the same genetically determined mechanisms as stereotypic chewing.
Insights
Selective breeding for methamphetamine-induced stereotyped chewing in mice revealed a genetic link. Low-chewing mice showed high circling and climbing, suggesting shared genetic mechanisms for these behaviors.
Area of Science:
- Neuroscience
- Behavioral Genetics
- Pharmacology
Background:
- Methamphetamine at high doses induces repetitive stereotypic behaviors in rodents.
- The heritability of these methamphetamine-induced behaviors suggests a genetic component.
Purpose of the Study:
- To investigate if selective breeding for high (HMA) and low (LMA) methamphetamine-induced stereotyped chewing affects other behaviors.
- To explore the genetic underpinnings of different stereotypic behaviors induced by methamphetamine.
Main Methods:
- Selective breeding of B6D2F2 mice for four generations based on methamphetamine-induced chewing.
- Assessing stereotypic behaviors (chewing, circling, climbing) and other responses to methamphetamine in HMA and LMA mice.
- Utilizing videotape analysis, automated activity monitors, and climbing assays across different methamphetamine doses.
Main Results:
- Low-chewing (LMA) mice displayed high levels of stereotyped circling and climbing.
- High-chewing (HMA) mice exhibited the opposite pattern, with low circling and climbing.
- Most other measured behaviors showed drug effects but no significant differences between the selected lines.
Conclusions:
- Stereotyped chewing, circling, and climbing behaviors share at least some common genetic mechanisms.
- These findings indicate that different stereotypic behaviors may not all be governed by the same genetic pathways.