Strain differences in the reverse tolerance to methamphetamine and changes in catecholaminergic neurons in mice

Area of Science:

• Neuroscience
• Pharmacology
• Behavioral Science

Background:

• Methamphetamine (MAP) is a potent psychostimulant with known effects on motor activity and neurochemistry.
• Individual differences in response to MAP, including susceptibility and neurochemical adaptations, are observed across different mouse strains.

Purpose of the Study:

• To investigate the effects of repeated methamphetamine administration on ambulatory activity and neurochemical changes in catecholaminergic neurons.
• To compare the susceptibility and neurochemical responses to MAP between dd and C57BL/6 mouse strains.

Main Methods:

• Repeated subcutaneous administration of MAP (2 mg/kg) to dd and C57BL/6 male mice over 4-day intervals.
• Assessment of ambulatory activity and quantification of neurochemical changes, including 3H-spiperone and 3H-WB4101 binding sites and catecholamine turnover.

Main Results:

• Single MAP administration markedly increased ambulatory activity in both mouse strains.
• Repeated MAP administration progressively enhanced ambulatory activity (reverse tolerance) without inducing stereotyped behaviors.
• dd mice exhibited higher susceptibility to MAP's effects and reverse tolerance compared to C57BL/6 mice.
• MAP treatment decreased catecholamine binding site densities and increased catecholamine turnover, particularly in dd mice.

Conclusions:

• The ambulation-increasing effect of MAP is positively correlated with catecholamine turnover and negatively with catecholamine binding site densities.
• The enhancing effect of MAP is partly mediated by alterations in brain catecholaminergic systems, specifically increased catecholamine turnover.
• Strain differences in neurochemical profiles influence susceptibility and response to repeated MAP administration.