Consequences of Neurotoxin-Induced Dopamine Loss on Striatal Synaptic Plasticity

Abstract

Synaptic plasticity refers to the ability of synapses to strengthen and weaken in response to changes in activity and is a neural correlate of learning and memory. In this chapter, the effects of dopamine signaling on striatal efferent neuron function and striatal synaptic plasticity are discussed, with a particular emphasis on how neurotoxin-induced dopamine loss alters plasticity. Multiple lines of evidence suggest that phasic dopamine signaling preferentially affects the function of dopamine D1 receptor-expressing spiny efferent neurons (D1-MSNs) and that the function of these neurons is disrupted by methamphetamine (METH)-induced dopamine neurotoxicity. Although dopamine signaling bidirectionally mediates long-term striatal plasticity, in general, dopamine D1 receptors promote long-term potentiation (LTP), whereas dopamine D2 receptors promote long-term depression (LTD). Research suggests that full dopamine lesions impair both striatal LTP and LTD. In contrast, partial dopamine loss specifically impairs dopamine D1 receptor-dependent LTP. The effects of methamphetamine (METH)-induced neurotoxicity on striatal plasticity have not been specifically tested. However, how METH-induced partial dopamine loss likely impairs striatal LTP is discussed in this chapter. Finally, the therapeutic potential of two dopaminergic drugs, l-3,4-dihydroxyphenylalanine (L-DOPA) and bupropion, to improve deficits arising from METH-induced dopamine neurotoxicity and thus improving therapeutic management of METH use disorder is considered.