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Methamphetamine-induced dopamine and serotonin reductions in neostriatum are not gender specific in rats with
M Fukumura1, G D Cappon, H W Broening
1Children's Hospital Research Foundation and Department of Pediatrics, University of Cincinnati, OH 45229-3039, USA.
Abstract:
Methamphetamine (MA)-induced monoamine depletions in male and female Sprague-Dawley CD rats were studied under conditions in which the magnitude of MA-induced hyperthermia was comparable between the sexes. MA (5 or 10 mg/kg) or saline (3 ml/kg) was administered SC four times at 2-h intervals. Animals were sacrificed 3 days posttreatment for the determination of dopamine (DA), serotonin (5-HT), and metabolites. MA induced significant monoamine reductions but the magnitude of these reductions was not significantly different between males and females. In the MA 5 mg/kg groups, neostriatal DA content was reduced by 51.2% and 44.8%, whereas 5-HT content was reduced by 30.6% and 23.9% of controls for males and females, respectively. In the MA 10 mg/kg groups, neostriatal DA content was reduced by 72.9% and 65.8%, whereas striatal 5-HT content was reduced by 77.4% and 73.6% of controls for males and females, respectively. No significant differences in thermal responses to MA were observed between genders. Unlike reports in mice, gender does not play a role in MA-induced monoamine reductions in rat neostriatum when MA-induced hyperthermia is comparable across sexes. The data also showed a threshold effect in which dopamine depletions were not correlated with hyperthermia at core body temperatures above approximately 41 degrees C.
Insights
Gender does not affect methamphetamine-induced monoamine depletions in rats when hyperthermia is similar. Dopamine depletions showed a threshold effect not directly correlated with hyperthermia above 41°C.
Area of Science:
- Neuroscience
- Pharmacology
- Toxicology
Background:
- Methamphetamine (MA) is known to cause depletions in monoamine neurotransmitters like dopamine and serotonin.
- Previous studies, particularly in mice, suggested gender differences in MA's neurotoxic effects.
Purpose of the Study:
- To investigate if gender influences MA-induced monoamine depletions in Sprague-Dawley CD rats.
- To examine the relationship between MA-induced hyperthermia and monoamine depletions across sexes.
Main Methods:
- Rats (male and female) received multiple subcutaneous administrations of MA (5 or 10 mg/kg) or saline.
- Monoamine levels (dopamine, serotonin) and their metabolites were measured in the neostriatum 3 days post-treatment.
- Core body temperature was monitored to ensure comparable hyperthermia between sexes.
Main Results:
- MA significantly reduced dopamine and serotonin levels in both male and female rats.
- No significant differences in the magnitude of monoamine depletions were observed between genders when hyperthermia was comparable.
- A threshold effect was noted, with dopamine depletions not correlating with hyperthermia above approximately 41°C.
Conclusions:
- In rats, gender does not appear to be a significant factor in MA-induced neostriatal monoamine depletions under conditions of similar hyperthermia.
- These findings contrast with some reports in mice, highlighting species-specific responses.
- The study identified a potential threshold for hyperthermia above which dopamine depletions may not be directly linked to temperature elevation.