Search bioRxiv⌕ Search

Biology subjects

Driscoll, G. S.

Publications and source records attributed to Driscoll, G. S..

2 recordsLinked to original sources

Dopamine and calcium dynamics in the nucleus accumbens core during food seeking

Extinction-reinstatement paradigms have been used to study reward seeking for both food and drug rewards. The nucleus accumbens is of particular interest in reinstatement due to its ability to energize motivated behavior. Indeed, previous work has demonstrated that suppression of neuronal activity or dopaminergic signaling in the nucleus accumbens reduces reinstatement to food seeking. In this study, we sought to further establish a connection between glutamatergic input, measured by proxy via a genetically encoded calcium indicator, and dopamine (DA) tone, measured simultaneously with a red-shifted DA biosensor. We performed this sensor multiplexing in the nucleus accumbens core in the classic extinction-reinstatement paradigm with food reward. We detected DA transients that changed in magnitude and/or temporally shifted over the course of self-administration training. In our calcium traces we observed a decrease from baseline time-locked to the lever press for food reward, which became more prominent with training. Both patterns were reduced in the first session of extinction with no deflections from baseline detected in either the DA or calcium traces in the last extinction session. When we recorded during reinstatement tests, bootstrapping analysis detected a calcium response when reinstatement was primed by cue or pellet+cue presentation, while a DA response was detected for pellet+cue reinstatement. These data further establish a role for nucleus accumbens core activity and DA in reinstatement of food seeking and represent the first attempt to simultaneously record the two during an extinction-reinstatement task.

neuroscience↗

Sex-specific behavioral and thalamo-accumbal circuit adaptations after oxycodone abstinence.

Opioid use disorder is characterized by compulsive drug seeking and heightened relapse vulnerability following abstinence, a phenomenon known as incubation of craving. Although preclinical data suggest similar behavioral expression of opioid use between sexes, conclusive evidence on sex differences in craving and relapse across abstinence periods remains lacking. Here, we investigated the effects of abstinence from oxycodone self-administration on neurotransmission in the paraventricular thalamus (PVT) to nucleus accumbens shell (NAcSh) pathway in male and female rats. Using optogenetics and ex vivo electrophysiology, we assessed synaptic strength, glutamate release probability, and intrinsic excitability of NAcSh medium spiny neurons (MSNs) following 1 (acute) or 14 (prolonged) days of forced abstinence. No sex differences were observed in oxycodone self-administration or somatic withdrawal. However, females exhibited greater cue-induced relapse after prolonged but not acute abstinence. Prolonged abstinence produced comparable increases in PVT-NAcSh synaptic strength and presynaptic glutamate release probability in both sexes, while inhibitory transmission and MSN excitability were largely unaltered. The dissociation between comparable circuit-level plasticity and sex-specific relapse vulnerability suggests that PVT-NAcSh strengthening represents a shared neuroadaptation to oxycodone abstinence, while mechanisms driving heightened relapse in females likely involve additional circuit elements that remain to be identified.

neuroscience↗