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Published on: January 22, 2016
Comparison of single-dose and extended methamphetamine administration on reversal learning in rats
Alisa R Kosheleff1, Danilo Rodriguez, Steve J O'Dell
1Department of Psychology, California State University, Los Angeles, 5151 State University Drive, Los Angeles, CA 90032, USA.
Rationale:
Protracted use of methamphetamine (mAMPH) can result in long-term impairments in cognitive function in humans. A previous study reported reversal-specific learning impairments in rats after a binge administration of mAMPH. Several studies show that extended exposure to mAMPH may confer protection against cognitive impairments and the insult to monoamine systems typically observed after larger binge doses.
Objectives:
To explore this issue, we compared the effects of escalating and single doses of mAMPH (and saline, SAL) on retention, reversal learning, and post-mortem analysis of dopamine and serotonin transporters, DAT and SERT.
Methods:
Rats learned to discriminate equiluminant stimuli and then were treated with either: (1) 4 weeks of mAMPH increasing by 0.3 mg/kg, culminating in 6 mg/kg (mAMPH(escal)); (2) 4 weeks of SAL with a single dose of 6 mg/kg on the last day of treatment (mAMPH(single)); or (3) 4 weeks of SAL. Following treatment, rats were tested on retention and reversal learning, with subsequent analysis of DAT and SERT binding across subregions of the striatum and frontoparietal cortex, respectively.
Results:
Retention of the pretreatment discrimination was not significantly impaired in either mAMPH treatment group. A significant decrease in ventrolateral striatal DAT binding was observed only in the mAMPH(single) group and frontoparietal SERT was unaffected by either mAMPH treatment. Both treatment groups demonstrated attenuated reversal learning, particularly on measures of accuracy and effort.
Conclusions:
These results show that extended and single-dose pretreatment with mAMPH similarly and selectively affect reversal learning, even in the absence of significant DAT or SERT changes.
Insights
Methamphetamine (mAMPH) exposure impairs reversal learning in rats, regardless of dose escalation. This cognitive deficit occurs without significant changes to dopamine or serotonin transporters, suggesting a complex neurobiological mechanism.
Area of Science:
- Neuroscience
- Cognitive Science
- Pharmacology
Background:
- Methamphetamine (mAMPH) use can lead to long-term cognitive impairments.
- Previous research indicates reversal-specific learning deficits after mAMPH binge administration.
- Extended mAMPH exposure may offer protection against cognitive deficits and monoamine system damage from high doses.
Purpose of the Study:
- To investigate the effects of escalating versus single doses of mAMPH on cognitive functions.
- To analyze the impact of mAMPH on dopamine transporter (DAT) and serotonin transporter (SERT) binding.
- To compare learning and memory retention after different mAMPH treatment regimens.
Main Methods:
- Rats were trained on a discrimination task and then received either escalating mAMPH, a single high dose of mAMPH, or saline for four weeks.
- Cognitive performance was assessed through retention and reversal learning tests.
- Post-mortem analysis examined DAT and SERT binding in specific brain regions, including the striatum and frontoparietal cortex.
Main Results:
- Neither mAMPH treatment group showed significant impairment in retention of the learned discrimination.
- A significant decrease in ventrolateral striatal DAT binding was found only in the single-dose mAMPH group.
- Both mAMPH treatment groups exhibited attenuated reversal learning, particularly in accuracy and effort.
Conclusions:
- Extended and single-dose mAMPH pretreatment similarly impair reversal learning.
- These cognitive effects manifest independently of significant changes in DAT or SERT binding.
- The findings suggest a selective impact of mAMPH on specific cognitive processes beyond transporter levels.
