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Blockade of dopamine D2 receptors disrupts intrahippocampal connectivity and enhances pain‐related working memory deficits in neuropathic pain rats
Author(s) -
CardosoCruz H.,
Dourado M.,
Monteiro C.,
Galhardo V.
Publication year - 2018
Publication title -
european journal of pain
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.305
H-Index - 109
eISSN - 1532-2149
pISSN - 1090-3801
DOI - 10.1002/ejp.1186
Subject(s) - neuroscience , dopamine receptor d2 , dopaminergic , psychology , dopamine , neuropathic pain , hippocampal formation , hippocampus , chronic pain , medicine
Background Dopamine ( DA ) is thought to be important to local hippocampal networks integrity during spatial working memory ( sWM ) processing. Chronic pain may contribute to deficient dopaminergic signalling, which may in turn affect cognition. However, the neural mechanisms that determine this impairment are poorly understood. Here, we evaluated whether the sWM impairment characteristic of animal models of chronic pain is dependent on DA D2 receptor (D2r) activity. Methods To address this issue, we implanted multichannel arrays of electrodes in the dorsal and ventral hippocampal CA 1 field (dv CA 1) of rats and recorded the neuronal activity during a classical delayed food‐reinforced T‐maze sWM task. Within‐subject behavioural performance and patterns of dorsoventral neural activity were assessed before and after the onset of persistent neuropathic pain using the spared nerve injury ( SNI ) model. Results Our results show that the peripheral nerve lesion caused a disruption in sWM and hippocampus spike activity and that disruption was maximized by the systemic administration of the D2r antagonist raclopride. These deficits are strictly correlated with a selective disruption of hippocampal theta‐ oscillations. Particularly, we found a significant decrease in intrahippocampal CA 1 field connectivity level. Conclusions Together, these results suggest that disruption of the dopaminergic balance in the intrahippocampal networks may be important for the development of cognitive deficits experienced during painful conditions. Significance This study provides new insights into the role of D2r in the manifestation of pain‐related sWM deficits. Our findings support that selective blockade of D2r produces a significant decrease in intrahippocampal connectivity mediated by theta ‐oscillations, and amplifies pain‐related sWM deficits. These results suggest that further characterization of intrahippocampal dopaminergic modulation may be clinically relevant for the understanding of cognitive impairments that accompanies nociceptive stressful conditions.