Gene-Targeted, CREB-Mediated Induction of ΔFosB Controls Distinct Downstream Transcriptional Patterns Within D1 and D2 Medium Spiny Neurons

CREB Binding at the Zfp189 Promoter Within Medium Spiny Neuron Subtypes Differentially Regulates Behavioral and Physiological Adaptations Over the Course of Cocaine Use

“…To understand the MSN subtypes responsible for this phenomenon, we adapted our viral delivery strategy to utilize Cre-dependent (loxP-STOP-loxP [LSL]) expression vectors to facilitate CRISPR-mediated CREB-Zfp189 interaction in an MSN-subtype-dependent manner. This approach has been previously applied by our group (22), and as in this earlier work, we see Zfp189 activation preferentially in NAc neurons that are conditionally expressing our CRISPR constructs (Supp. Fig.…”

“…We utilized modified CRISPR constructs which we have described previously (19,22), and are described in more detail in the Supplement.…”

“…2a). This approach has been validated and applied by our group to the Zfp189 locus in prefrontal cortex (PFC) neurons to study stressrelated behaviors (19) and the Fosb locus in the NAc to study medium spiny neuron (MSN)specific transcriptional responses (22).…”

Sex differences in methamphetamine use disorder perused from pre-clinical and clinical studies: Potential therapeutic impacts

“…Voluntary oral METH administered female mice exhibited increased Oprk1 and decreased memory protein marker, protein kinase M zeta (PKMζ), in the hippocampus ( Avila et al, 2021 ). Taken together, these observations suggest that sexual dimorphism in METH SA-induced changes in gene expression may be secondary to sex-dependent differences in the basal levels of certain genes and proteins that might impact behavioral responses after repeated exposure to an identical substance ( Cadet, 2021 ) or might be regulated to an identical transcription factor ( Lardner et al, 2021 ).…”

“…Immediately early genes and proteins are thought to participate in the regulation of the long-term behavioral effects of rewarding drugs including opioid and psychostimulant substances ( Bisagno and Cadet, 2019 ; Cadet, 2021 ; Lardner et al, 2021 ). It was therefore of interest to test whether these were affected by METH in a sexually dimorphic fashion.…”