Amperometric measurements of cocaine cue and novel context-evoked glutamate and nitric oxide release in the nucleus accumbens core.

Abstract:

:Cue-induced reinstatement of cocaine seeking after self-administration (SA) and extinction relies on glutamate release in the nucleus accumbens core (NAcore), which activates neuronal nitric oxide synthase interneurons. Nitric oxide (NO) is required for structural plasticity in NAcore medium spiny neurons, as well as cued cocaine seeking. However, NO release in the NAcore during reinstatement has yet to be directly measured. Furthermore, the temporal relationship between glutamate release and the induction of an NO response also remains unknown. Using wireless amperometric recordings in awake behaving rats, we quantified the magnitude and temporal dynamics of novel context- and cue-induced reinstatement-evoked glutamate and NO release in the NAcore. We found that re-exposure to cocaine-conditioned stimuli following SA and extinction increased extracellular glutamate, leading to release of NO in the NAcore. In contrast, exposing drug-naïve rats to a novel context led to a lower magnitude rise in glutamate in the NAcore relative to cue-induced reinstatement. Interestingly, novel context exposure evoked a higher magnitude NO response relative to cue-induced reinstatement. Despite differences in magnitude, novel context evoked-NO release in the NAcore was also temporally delayed when compared to glutamate. These results demonstrate a dissociation between the magnitude of cocaine cue- and novel context-evoked glutamate and NO release in the NAcore, yet similarity in the temporal dynamics of their release. Together, these data contribute to a greater understanding of the relationship between glutamate and NO, two neurotransmitters implicated in encoding the valence of distinct contextual stimuli.

journal_name

J Neurochem

authors

Siemsen BM,McFaddin JA,Haigh K,Brock AG,Nan Leath M,Hooker KN,McGonegal LK,Scofield MD

doi

10.1111/jnc.14952

subject

Has Abstract

pub_date

2020-06-01 00:00:00

pages

599-616

issue

5

eissn

0022-3042

issn

1471-4159

journal_volume

153

pub_type

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