Accepted for publication (PostPrint)
Experimental and Clinical Psychopharmacology
Attention deficits and inappropriate regulation of sensory signal processing are hallmarks of many neuropsychiatric conditions, including attention deficit hyperactivity disorder (ADHD), for which methylphenidate (MPH) and atomoxetine (ATX) are commonly prescribed therapeutic treatments. Despite their widespread use and known mechanism of blocking reuptake of catecholamine transmitters in the brain, the resultant actions on individual neuron and neural circuit function that lead to therapeutic efficacy are poorly understood. Given the ability of MPH and ATX to improve cognitive performance in humans and rodent assays of attention, we were interested in their influence on early sensory processing in the dorsal lateral geniculate nucleus (dLGN), the primary thalamic relay for visual information from the retina to the visual cortex. In male rats, dLGN neuronal responses to light stimuli were altered in multiple ways following doses of MPH or ATX observed to enhance performance in visually-guided assays of attention in rats (MPH, 2 mg/kg; ATX, 0.5 mg/kg). Latencies to response onset and to the peak of the primary response were decreased, while the peak intensity and area of the primary response were increased. In addition, some cells that were unresponsive to light stimuli prior to drug treatment displayed a ‘gating effect,’ wherein prominent responses to light stimuli were evident following drug administration. Our results begin to reveal unique effects of MPH and ATX in enhancing sensory signal transmission through visual circuitry, and may yield new insights for understanding the pathophysiology of certain cognitive disorders and inform development of improved therapeutic treatments for these conditions.
Navarra, Rachel; Clark, Brian; Zitnik, Gerard; and Waterhouse, Barry, "Methylphenidate and Atomoxetine Enhance Sensory-Evoked Neuronal Activity in the Visual Thalamus of Male Rats" (2013). School of Osteopathic Medicine Faculty Scholarship. 28.
Navarra RL, Clark BD, Zitnik GA, Waterhouse BD. Methylphenidate and Atomoxetine Enhance Sensory-Evoked Neuronal Activity in the Visual Thalamus of Male Rats. Exp Clin Psychopharmacol. 2013 Oct;21(5):363-74. doi: 10.1037/a0033563. PMID: 24099357. PMCID: PMC5127596.