Repeated exposure to methiopropamine increases dendritic spine density in the rat nucleus accumbens core

Repeated exposure to classical psychomotor stimulants, like amphetamine (AMPH), produces locomotor sensitization and accompanied structural plasticity of dendritic spines in the nucleus accumbens (NAcc). Following our previous report that repeated administration of methiopropamine (MPA), a structural analog to meth-AMPH, produces locomotor sensitization, it was examined in the present study whether this behavioral change also accompanies with structural plasticity in the NAcc in a similar way to AMPH. A week after adeno-associated viral vectors containing enhanced green fluorescent protein (eGFP) were microinjected into the NAcc core, rats were repeatedly injected with saline, AMPH (1 mg/kg, IP), or MPA (5 mg/kg, IP) once every 2-3 days for a total of 4 times. Two weeks after last injection, all rats were perfused and their brains were processed for immunohistochemical staining. The image stacks for dendrite segments of medium spiny neuronal cells in the NAcc core were obtained and dendritic spines were quantitatively analyzed. Interestingly, it was found that the number of total spine density, with thin spine as a major contributor, was significantly increased in MPA compared to saline pre-exposed group, in a similar way to AMPH. These results indicate that MPA, a novel psychoactive substance, has similar characteristics with AMPH in that they both produce structural as well as behavioral changes, further supporting MPA's dependence and abuse potential.