Nicotine but not saline self-administering or yoked control conditions produces sustained neuroadaptations in the accumbens shell

Abstract

IntroductionUsing yoked animals as the control when monitoring operant drug-self-administration is considered the golden standard. However, instrumental learning per se recruits several neurocircuits that may produce distinct or overlapping neuroadaptations with drugs of abuse. The aim of this project was to assess if contingent responding for nicotine or saline in the presence of a light stimulus as a conditioned reinforcer is associated with sustained neurophysiological adaptations in the nucleus accumbens shell (nAcS), a brain region repeatedly associated with reward related behaviors.MethodsTo this end, nicotine-or saline-administrating rats and yoked-saline stimulus-unpaired training conditions were assessed in operant boxes over four consecutive weeks. After four additional weeks of home cage forced abstinence and subsequent cue reinforced responding under extinction conditions, ex vivo electrophysiology was performed in the nAcS medium spiny neurons (MSNs).ResultsWhole cell recordings conducted in voltage and current-clamp mode showed that excitatory synapses in the nAcS were altered after prolonged forced abstinence from nicotine self-administration. We observed an increase in sEPSC amplitude in animals with a history of contingent nicotine SA potentially indicating higher excitability of accumbal MSNs, which was further supported by current clamp recordings. Interestingly no sustained neuroadaptations were elicited in saline exposed rats from nicotine associated visual cues compared to the yoked controls.ConclusionThe data presented here indicate that nicotine self-administration produces sustained neuroadaptations in the nAcS while operant responding driven by nicotine visual stimuli has no long-term effects on MSNs in nAcS.

Subregion specific neuroadaptations in the female rat striatum during acute and protracted withdrawal from nicotine

“…Considering that PPR was not significantly modulated by treatment it is thus likely that the increased excitability is associated with changes in AMPA receptor subunit composition or increased AMPA receptor density, thereby strengthening AMPA receptor signaling. Importantly, increased excitatory neurotransmission and AMPA receptor expression has previously been demonstrated in male rats following nicotine self-administration (Domi et al 2023b ; Gipson et al 2013 ), and may thus be an important neurobiological underpinning of nicotine addiction (Ruda-Kucerova et al 2021 ).…”

Mifepristone decreases nicotine intake in dependent and non-dependent adult rats

“…In the present study, control rats that self-administered saline were not included. However, it should be noted that operant responding for saline is very low, even when visual cues are presented concomitant with the saline infusions (Chellian et al, 2021a; Domi et al, 2023; Jin et al, 2020). In the present study, the rats were single-housed.…”

Pre- and postsynaptic signatures in the prelimbic cortex associated with “alcohol use disorder” in the rat

“…Layer 2/3 PL pyramidal neurons were visualized under infrared-differential interference contrast with a Nikon Eclipse FN1 microscope. Recording pipettes (resistance 2.5 to 5.5 MΩ) were filled with internal solution containing (in mM): 135 K-Glu, 20 KCl, 2 MgCl2, 0.1 EGTA, 10 Hepes, 2 Mg-ATP and 0.3 Na-GTP, with pH adjusted to 7.3 with KOH, and osmolarity to 295 mOsm with sucrose [37]. To record spontaneous excitatory postsynaptic currents (sEPSCs) in voltage clamp mode, neurons were clamped at −65 mV using MultiClamp 700B amplifier, digitized at 10 kHz and filtered at 2 kHz using Clampex.…”