Amphetamine's dose-dependent effects on dorsolateral striatum sensorimotor neuron firing

Abstract

Amphetamine elicits motoric changes by increasing the activity of central neurotransmitters such as dopamine and serotonin, but how these neurochemical signals are transduced into motor commands is unclear. The dorsolateral striatum (DLS), a component of the cortico-subcortical reentrant motor loop, contains abundant neurotransmitter transporters that amphetamine could affect. It has been hypothesized that DLS medium spiny neurons contribute to amphetamine’s motor effects. To study striatal activity contributing to amphetamine-induced movements, activity of DLS neurons related to vertical head movement was recorded while tracking head movements before and after acute amphetamine injection. Relative to saline, all amphetamine doses induced head movements above pre-injection levels, revealing an inverted U-shaped dose-response function. Lower doses (1mg/kg and 2 mg/kg, intraperitoneal) induced a greater number of long (distance and duration) movements than the high dose (4 mg/kg), which induced stereotypy. Firing rates (FR) of individual head movement neurons were compared before and after injection during similar head movements, defined by direction, distance, duration, and apex. Changes in FR induced by amphetamine were co-determined by dose and pre-injection FR of the neuron. Specifically, all doses increased the FRs of slower firing neurons but decreased the FRs of faster firing neurons. The magnitudes of elevation or reduction were greater at lower doses, but less pronounced at the high dose, forming an inverted U function. Modulation of DLS firing may interfere with sensorimotor processing. Furthermore, pervasive elevation of slow firing neurons’ FRs may feed-forward and increase excitability in thalamocortical premotor areas, contributing to the increased movement initiation rate.

Automated touch screen device for recording complex rodent behaviors

“…Interestingly we also found a correlation between amphetamine treatment and increased step velocity. This is in line with a recent report showing that amphetamine increases the velocity of head movements in rats (Ma et al, 2013). These data suggest that amphetamine does not increase step lengths, nor does it only grossly increase movement (as recorded by distance traveled), but that it appears to specifically affect the quantity and rate at which steps are taken.…”

Electrophysiological evidence of alterations to the nucleus accumbens and dorsolateral striatum during chronic cocaine self‐administration

“…Thus, the maintenance of unabated sensorimotor firing during chronic cocaine self‐administration probably represents an important difference in on‐drug striatal processing as compared to processing natural rewards. This finding suggests that the pharmacological dose‐dependent enhancement of most striatal FR in response to acute cocaine (Pederson et al ., ; Tang et al ., ; Pawlak et al ., ) or amphetamine (Ma et al ., ) is a response that persists throughout repeated exposure.…”

An Argument for Amphetamine-Induced Hallucinations in an Invertebrate

“…First, the AMPH-induced swims in intact animals, and the corresponding AMPH-induced motor programs in isolated brains occur sporadically and without warning in the minutes to hours after AMPH administration, much as hallucinations of varied causes do in humans. Second, while AMPH can produce elevated excitability in vertebrate neurons ( Jahromi et al, 1991 ; Ma et al, 2013 ), its effect on Tritonia’s S-cells is of particular interest due to its sporadic nature. Even when tested in 0 Ca 2+ saline, where spike-mediated synaptic inputs can play no role, Tritonia’s AMPH-induced S-cell plateau potentials occurred on some test depolarizations and not on others.…”