ArticleNeuropsychopharmacology : official publication of the American College of Neuropsychopharmacology2021
Prelimbic cortical projections to rostromedial tegmental nucleus play a suppressive role in cue-induced reinstatement of cocaine seeking.
Article in Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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9 citing papers in PubMed.
- Uncovering phenotypic diversity and cell-type-specific prefrontal cortex calcium dynamics in rat fentanyl self-administration.bioRxiv : the preprint server for biology · 2026Article
- Prelimbic cortex to ventral tegmental area projection regulates early social isolation stress-potentiated heroin seeking in mice.Nature communications · 2025Article
- GABAMedComm · 2025Review
- Chronic ethanol exposure produces long-lasting, subregion-specific physiological adaptations in RMTg-projecting mPFC neurons.Neuropharmacology · 2024Article
- Single-nucleus genomics in outbred rats with divergent cocaine addiction-like behaviors reveals changes in amygdala GABAergic inhibition.Nature neuroscience · 2023Article
- Pumping the brakes: rostromedial tegmental inhibition of compulsive cocaine seeking.bioRxiv : the preprint server for biology · 2023Article
- Involvement of cortical input to the rostromedial tegmental nucleus in aversion to foot shock.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2023Article
- The roles of rat medial prefrontal and orbitofrontal cortices in relapse to cocaine-seeking: A comparison across methods for identifying neurocircuits.Addiction neuroscience · 2022Article
- Monosynaptic Retrograde Tracing From Prelimbic Neuron Subpopulations Projecting to Either Nucleus Accumbens Core or Rostromedial Tegmental Nucleus.Frontiers in neural circuits · 2021Article
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Abstract
The prelimbic (PL) region of prefrontal cortex has been implicated in both driving and suppressing cocaine seeking in animal models of addiction. We hypothesized that these opposing roles for PL may be supported by distinct efferent projections. While PL projections to nucleus accumbens core have been shown to be involved in driving reinstatement of cocaine seeking, PL projections to the rostromedial tegmental nucleus (RMTg) may instead suppress reinstatement of cocaine seeking, due to the role of RMTg in behavioral inhibition. Here, we used a functional disconnection approach to temporarily disrupt the PL-RMTg pathway during cue- or cocaine-induced reinstatement. Male Sprague Dawley rats self-administered cocaine during daily 2-h sessions for ≥10 days and then underwent extinction training. Reinstatement of extinguished cocaine seeking was elicited by cocaine-associated cues or cocaine prime. Prior to reinstatement, rats received microinjections of the GABA agonists baclofen/muscimol (1/0.1 mM) into unilateral PL and the AMPA receptor antagonist NBQX (1 mM) into contralateral or ipsilateral RMTg. Functional disconnection of PL-RMTg via contralateral inactivation markedly increased cue-induced reinstatement, but did not increase cocaine-induced reinstatement or drive reinstatement of extinguished cocaine seeking in the absence of cues or cocaine. Enhanced cue-induced reinstatement was also observed with ipsilateral inactivation of PL and RMTg, but not with unilateral inactivation of PL or RMTg alone, indicating that both ipsilateral and contralateral projections from PL to RMTg have an inhibitory influence on behavior. These data further support a suppressive role for PL in cocaine seeking by implicating PL efferent projections to RMTg in inhibiting cue-induced reinstatement.
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