RT Journal Article
SR Electronic
T1 Dopamine D2 Receptors in the Paraventricular Thalamus Attenuate Cocaine Locomotor Sensitization
JF eneuro
JO eNeuro
FD Society for Neuroscience
SP ENEURO.0227-17.2017
DO 10.1523/ENEURO.0227-17.2017
A1 Abigail Clark
A1 Felix Leroy
A1 Kelly M. Martyniuk
A1 Wendy Feng
A1 Erika McManus
A1 Matthew Bailey
A1 Jonathan Javitch
A1 Peter Balsam
A1 Christoph Kellendonk
YR 2017
UL http://www.eneuro.org/content/early/2017/10/12/ENEURO.0227-17.2017.abstract
AB Alterations in thalamic dopamine or dopamine D2 receptors (D2R) have been measured in drug addiction and schizophrenia, but the relevance of thalamic D2Rs for behavior is largely unknown. Using in situ hybridization and mice expressing green fluorescent protein (GFP) under the Drd2 promoter, we found that D2R expression within the thalamus is enriched in the paraventricular nucleus (PVT) as well as in more ventral midline thalamic nuclei. Within the PVT, D2Rs are inhibitory as their activation inhibits neuronal action potentials in brain slices. Using Cre-dependent anterograde and retrograde viral tracers, we further determined that PVT neurons are reciprocally interconnected with multiple areas of the limbic system including the amygdala and the nucleus accumbens. Based on these anatomical findings, we analyzed the role of D2Rs in the PVT in behaviors that are supported by these areas and that also have relevance for schizophrenia and drug addiction. Male and female mice with selective overexpression of D2Rs in the PVT showed attenuated cocaine locomotor sensitization, whereas anxiety levels, fear conditioning, sensorimotor gating, and food-motivated behaviors were not affected. These findings suggest the importance of PVT inhibition by D2Rs in modulating the sensitivity to cocaine, a finding that may have novel implications for human drug use.Significance Statement Alterations in thalamic dopamine or D2 receptors (D2R) have been measured in drug addiction and schizophrenia. However, although D2Rs have been extensively studied in the striatum, the relevance of thalamic D2Rs for neuronal function as well as behavior is largely unclear. Therefore, the significance of the human imaging findings for psychiatric disorders is unclear. Here, we found that the midline thalamus displays enriched expression of D2Rs whose activation inhibits thalamic neuron activity. Overexpression of D2R in the paraventricular nucleus (PVT), a dorsal midline thalamic nucleus, attenuated cocaine locomotor sensitization. This suggests that D2R-mediated inhibition of the PVT modulates the sensitivity to cocaine, a finding which has potential relevance for human drug use.