ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2013
Cannabinoid transmission in the prelimbic cortex bidirectionally controls opiate reward and aversion signaling through dissociable kappa versus μ-opiate receptor dependent mechanisms.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 53 citations in OpenAlex.
- Heroin-induced neuroadaptations of CB1 receptors and their involvement in conditioned place preference.Psychopharmacology · 2026Article
- A Preliminary Investigation of Brain Cannabinoid Receptor Type 1 (CB1R) Availability in Men with Opioid Use Disorder.Research square · 2025Article
- Prenatal alcohol exposure dysregulates the expression of clock genes and alters rhythmic behaviour in mice.Open biology · 2025Article
- Dysregulation of the endogenous cannabinoid system following opioid exposure.Psychiatry research · 2023Review
- Optogenetic stimulation in the medial prefrontal cortex modulates stimulus valence from rewarding and aversive to neutral states.Frontiers in psychiatry · 2023Article
- Brain Penetrant, but not Peripherally Restricted, Synthetic Cannabinoid 1 Receptor Agonists Promote Morphine-Mediated Respiratory Depression.Cannabis and cannabinoid research · 2022Article
- Cannabinoids-Perspectives for Individual Treatment in Selected Patients: Analysis of the Case Series.Biomedicines · 2022Article
- Effects of combined THC and heroin vapor inhalation in rats.Psychopharmacology · 2022Article
- Anxiety and cognitive-related effects of ΔPsychopharmacology · 2022Article
- Cannabinoid Receptor Type 1 Regulates Drug Reward Behavior via Glutamate Decarboxylase 67 Transcription.International journal of molecular sciences · 2021Article
- The Paradoxical Effect Hypothesis of Abused Drugs in a Rat Model of Chronic Morphine Administration.Journal of clinical medicine · 2021Article
- Medial prefrontal cortex diclofenac-induced antinociception is mediated through GPR55, cannabinoid CB1, and mu-opioid receptors of this area and periaqueductal gray.Naunyn-Schmiedeberg's archives of pharmacology · 2020Article
- The Bivalent Rewarding and Aversive properties of ΔScientific reports · 2019Article
- The Lateral Habenula Directs Coping Styles Under Conditions of Stress via Recruitment of the Endocannabinoid System.Biological psychiatry · 2018Article
- The Role of Cholinergic Midbrain Neurons in Startle and Prepulse Inhibition.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2018Article
- Cannabinoid receptor-1 signaling contributions to sign-tracking and conditioned reinforcement in rats.Psychopharmacology · 2018Article
- Phytocannabinoids modulate emotional memory processing through interactions with the ventral hippocampus and mesolimbic dopamine system: implications for neuropsychiatric pathology.Psychopharmacology · 2018Review
- Emerging Evidence for Cannabis' Role in Opioid Use Disorder.Cannabis and cannabinoid research · 2018Review
- Cannabinoid reward and aversion effects in the posterior ventral tegmental area are mediated through dissociable opiate receptor subtypes and separate amygdalar and accumbal dopamine receptor substrates.Psychopharmacology · 2017Article
- Seeing through the smoke: Human and animal studies of cannabis use and endocannabinoid signalling in corticolimbic networks.Neuroscience and biobehavioral reviews · 2017Review
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 2 countries.
Funding
Abstract
Cannabinoid, dopamine (DA), and opiate receptor pathways play integrative roles in emotional learning, associative memory, and sensory perception. Modulation of cannabinoid CB1 receptor transmission within the medial prefrontal cortex (mPFC) regulates the emotional valence of both rewarding and aversive experiences. Furthermore, CB1 receptor substrates functionally interact with opiate-related motivational processing circuits, particularly in the context of reward-related learning and memory. Considerable evidence demonstrates functional interactions between CB1 and DA signaling pathways during the processing of motivationally salient information. However, the role of mPFC CB1 receptor transmission in the modulation of behavioral opiate-reward processing is not currently known. Using an unbiased conditioned place preference paradigm with rats, we examined the role of intra-mPFC CB1 transmission during opiate reward learning. We report that activation or inhibition of CB1 transmission within the prelimbic cortical (PLC) division of the mPFC bidirectionally regulates the motivational valence of opiates; whereas CB1 activation switched morphine reward signaling into an aversive stimulus, blockade of CB1 transmission potentiated the rewarding properties of normally sub-reward threshold conditioning doses of morphine. Both of these effects were dependent upon DA transmission as systemic blockade of DAergic transmission prevented CB1-dependent modulation of morphine reward and aversion behaviors. We further report that CB1-mediated intra-PLC opiate motivational signaling is mediated through a μ-opiate receptor-dependent reward pathway, or a κ-opiate receptor-dependent aversion pathway, directly within the ventral tegmental area. Our results provide evidence for a novel CB1-mediated motivational valence switching mechanism within the PLC, controlling dissociable subcortical reward and aversion pathways.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.