Parental THC exposure leads to compulsive heroin-seeking and altered striatal synaptic plasticity in the subsequent generation.
Henrietta Szutorisz, Jennifer A DiNieri, Eric Sweet, Gabor Egervari, Michael Michaelides, Jenna M Carter, Yanhua Ren, Michael L Miller, Robert D Blitzer, Yasmin L. Hurd
Neuropsychopharmacology May 2014 DOI: 10.1038/npp.2013.352 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Experimental animal study Peer reviewed |
|---|---|
| Population | Adult F1 offspring of rats exposed to THC during adolescence; the offspring were themselves unexposed to THC |
| Intervention | Δ(9)-tetrahydrocannabinol (THC) |
| Topics | Cannabis Neuroplasticity |
| Key findings | Parental adolescent THC exposure in rats was associated with increased work effort to self-administer heroin and enhanced stereotyped behaviors during acute withdrawal in unexposed adult offspring. In the dorsal striatum, offspring showed decreased mRNA and protein levels and reduced NMDA receptor binding, with altered excitatory synaptic plasticity. The authors suggest this could possibly confer enhanced risk for psychiatric disorders in the subsequent generation. |
Abstract
Recent attention has been focused on the long-term impact of cannabis exposure, for which experimental animal studies have validated causal relationships between neurobiological and behavioral alterations during the individual's lifetime. Here, we show that adolescent exposure to Δ(9)-tetrahydrocannabinol (THC), the main psychoactive component of cannabis, results in behavioral and neurobiological abnormalities in the subsequent generation of rats as a consequence of parental germline exposure to the drug. Adult F1 offspring that were themselves unexposed to THC displayed increased work effort to self-administer heroin, with enhanced stereotyped behaviors during the period of acute heroin withdrawal. On the molecular level, parental THC exposure was associated with changes in the mRNA expression of cannabinoid, dopamine, and glutamatergic receptor genes in the striatum, a key component of the neuronal circuitry mediating compulsive behaviors and reward sensitivity. Specifically, decreased mRNA and protein levels, as well as NMDA receptor binding were observed in the dorsal striatum of adult offspring as a consequence of germline THC exposure. Electrophysiologically, plasticity was altered at excitatory synapses of the striatal circuitry that is known to mediate compulsive and goal-directed behaviors. These findings demonstrate that parental history of germline THC exposure affects the molecular characteristics of the striatum, can impact offspring phenotype, and could possibly confer enhanced risk for psychiatric disorders in the subsequent generation.
Comparable studies
Other preclinical and animal studies on neuroplasticity, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Psychedelics promote neuroplasticity through the activation of intracellular 5-HT2A receptors In vitro and in vivo (rodent) models | 2023 | Experimental study | |
| Psychedelics promote plasticity by directly binding to BDNF receptor TrkB Mice | 2023 | Experimental study | |
| Effects of psilocybin on hippocampal neurogenesis and extinction of trace fear conditioning Mice | 2013 | Experimental study | |
| The alkaloids of Banisteriopsis caapi, the plant source of the Amazonian hallucinogen Ayahuasca, stimulate adult neurogenesis in vitro Progenitor cells from subventricular and subgranular zones of adult mice brains | 2017 | In vitro experimental study | |
| N,N-dimethyltryptamine compound found in the hallucinogenic tea ayahuasca, regulates adult neurogenesis in vitro and in vivo Mice | 2020 | In vitro and in vivo experimental study |
Citations in the library
Cited by 8
- Perturbation of 3D nuclear architecture, epigenomic dysregulation and aging, and cannabinoid synaptopathy reconfigures conceptualization of cannabinoid pathophysiology: part 1–aging and epigenomics Frontiers in Psychiatry September 5, 2023
- Age-Related Effects of Cannabis and Cannabinoids on Brain and Behavior. Cannabis and Cannabinoid Research April 2026
- Differential effects of cannabis constituents on schizophrenia-related psychosis: a rationale for incorporating cannabidiol into a schizophrenia therapeutic regimen Frontiers in Psychiatry April 23, 2024
- Cannabis and synaptic reprogramming of the developing brain. Nature Reviews Neuroscience July 2021
- High times for cannabis: Epigenetic imprint and its legacy on brain and behavior. Neuroscience & Biobehavioral Reviews February 2018
and 3 more in the library
Cites 9
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- Cannabinoid exposure in adolescent female rats induces transgenerational effects on morphine conditioned place preference in male offspring Journal of Psychopharmacology April 19, 2012
- An evidence based review of acute and long-term effects of cannabis use on executive cognitive functions. Journal of Addiction Medicine March 2011
- Adolescent cannabis use and psychosis: epidemiology and neurodevelopmental models British Journal of Pharmacology June 1, 2010
- Dynamic changes of the endogenous cannabinoid and opioid mesocorticolimbic systems during adolescence: THC effects. European Neuropsychopharmacology November 2008
and 4 more in the library