Abstract
The striatum is a forebrain nucleus required for the acquisition of appetitive reinforcement. Striatal structure and gross activation is abnormal in attention-deficit hyperactivity disorder (ADHD), a condition in which reinforcement-obtaining behaviour is altered, but it is currently unknown whether it is accompanied by abnormal striatal processing and output, or how the stimulant drugs used to treat ADHD modifies striatal neuron activity in disorder sufferers. This was addressed by recording pre- and post-amphetamine (AMPH) striatal single-unit activity from freely-moving genetically hypertensive (GH) rats, a putative animal model of ADHD, both as they rested, and during a contextually-signalled classical conditioning task. The isolation and characterisation of neuronal subtypes revealed that putative fast-spiking (pFS) interneuron activity was upregulated in resting GH rats, compared to the control Wistar (WI) strain. AMPH increased the activity of these cells in resting WI rats, but appeared to partially normalise GH rat pFS interneuron firing rate to that of pre-drug WI rats, an effect consistent with the ability of AMPH to treat ADHD symptoms. Of most interest in on-task animals were conditioned stimulus (CS) evoked modulations. Across all neurons, positive CS (CS+) encoding was less widespread than that evoked by the negative CS (CS-). Furthermore, the overall extent of CS+ encoding was particularly restricted in GH rats, and the amplitude of all CS+ related excitations was abnormally low in this strain. CS+ encoding was also less widespread in both strains when putative medium spiny (pMS) neurons were considered. CS+ encoding pMS neurons were not, however, abnormally rare in GH rats, although the amplitude of pMS neuron CS+ evoked excitations was reduced in this strain. AMPH abolished differential CS encoding in WI rats by reducing the overall extent of CS- encoding. In contrast, AMPH increased the extent of CS+ encoding in GH rats without disrupting differential CS encoding, both when all cells and only pMS neurons were included. This may represent a second therapeutic effect, particularly as CS+ encoding was abnormally sparse in GH rats when all recorded neurons were considered. The abnormal striatal neuron activity in GH rats may reflect processing deficits that underlie the expression of ADHD. Furthermore, the ability of AMPH to normalise aspects GH rat striatal neuron activity may provide insight into the means by which stimulant treatment is able to improve ADHD symptoms.