Prenatal Cannabis Exposure Increases Heroin Seeking with Allostatic Changes in Limbic Enkephalin Systems in Adulthood

Spano, Maria Sabrina; Ellgren, Maria; Wang, X.; Hurd, Yasmin L.

doi:10.1016/j.biopsych.2006.03.073

Cited by 136 publications

(133 citation statements)

References 196 publications

(222 reference statements)

Supporting

Mentioning

122

Contrasting

Order By: Relevance

“…In particular, CP increases the acquisition of morphine self-administration and decreases µ-opioid receptor functionality in the nucleus accumbens shell in males but not female animals [107]. In line with our results, decreased µ-opioid-coupled G-protein activity was found in the nucleus accumbens shell of male rats exposed prenatally to THC, with no changes in the nucleus accumbens core or caudate putamen [108]. Together, these data suggest that cannabinoid exposure in early stages of development and adolescence produces perdurable changes in µ-opioid receptor functionality that are specific to the nucleus accumbens shell, which is one of the brain regions most closely related to natural and drug-induced reward.…”

Section: Early Cannabis Consumption and The Risk Of Addiction To Othesupporting

confidence: 91%

Age-Dependent Effects of Cannabinoids on Neurophysiological, Emotional, and Motivational States

Viveros

Marco

2015

Cannabinoid Modulation of Emotion, Memory, and Motivation

View full text Add to dashboard Cite

Cannabis sativa preparations are among the illicit drugs most commonly used by young people, including pregnant women. The endocannabinoid (eCB) system, which is involved in the regulation of emotional and motivational homeostasis, synaptic plasticity and cognitive functions, also plays a critical role in diverse phases of brain development. Both perinatal and periadolescent periods are critical for brain eCB system development. Thus, interference of endocannabinoid signalling by cannabis exposure may contribute to explain the enduring negative impact of cannabis on neurodevelopmental processes and the resulting psycho-physio-pathological consequences. In the present chapter we describe and discuss published data dealing with the long-term neurobehavioural effects of cannabis exposure during the prenatal and adolescent periods. Human studies have demonstrated that marijuana consumption by pregnant women critically affects the neurobehavioural development of their children. Investigations using animal models provide useful information for a better understanding of the long-lasting deleterious consequences of cannabis exposure during pregnancy and lactation. Increasing use of cannabis among adolescents is a matter of great public concern that has led to a parallel increase in research on appropriate animal models. Chronic administration of cannabinoid agonists during the periadolescent period causes persistent behavioural alterations related to cognitive deficits, increased risk of psychosis, mood disorders and addiction to cannabis and other drugs of abuse. The underlying mechanisms by which cannabis use may lead to these disorders, including genetic vulnerability and the increasing content of the main psychoactive ingredient in cannabis preparations, delta-9-tetrahydrocannabinol (THC), will be discussed. To conclude, prevention and therapeutic strategies based on scientific knowledge will be proposed.

show abstract

Section: Early Cannabis Consumption and The Risk Of Addiction To Othesupporting

confidence: 91%

Age-Dependent Effects of Cannabinoids on Neurophysiological, Emotional, and Motivational States

Viveros

Marco

2015

Cannabinoid Modulation of Emotion, Memory, and Motivation

View full text Add to dashboard Cite

show abstract

“…The apparent relative enhancement of NAc shell PENK gene expression in THC animals even after repeated opiate exposure, which generally decreases PENK transcription (Georges et al, 1999;Uhl et al, 1988), suggests a persistent disturbance of the enkephalin reward system with early THC exposure. Long-term disturbance of the PENK system appears a common feature of early THC exposure since we have recently observed a similar selective increased PENK mRNA expression in the NAc of adult offspring with THC exposure limited to the prenatal period; these animals also showed increased heroin intake (Spano et al, 2006). THC stimulates CB 1 receptors, which similar to mORs, are coupled to Gi/o G-proteins (Pertwee and Ross, 2002) that should inhibit PENK transcription.…”

Section: Discussionmentioning

confidence: 72%

Adolescent Cannabis Exposure Alters Opiate Intake and Opioid Limbic Neuronal Populations in Adult Rats

Ellgren

Spano

Hurd

2006

Neuropsychopharmacol

Self Cite

261

208

View full text Add to dashboard Cite

Cannabis use is a hypothesized gateway to subsequent abuse of other drugs such as heroin. We currently assessed whether D-9-tetrahydrocannabinol (THC) exposure during adolescence modulates opiate reinforcement and opioid neural systems in adulthood. Long-Evan male rats received THC (1.5 mg/kg intraperitoneally (i.p.)) or vehicle every third day during postnatal days (PNDs) 28-49. Heroin self-administration behavior (fixed ratio-1; 3-h sessions) was studied from young adulthood (PND 57) into full adults (PND 102). THC-pretreated rats showed an upward shift throughout the heroin self-administration acquisition (30 mg/kg/infusion) phase, whereas control animals maintained the same pattern once stable intake was obtained. Heightened opiate sensitivity in THC animals was also evidenced by higher heroin consumption during the maintenance phase (30 and 60 mg/kg/infusion) and greater responding for moderate-low heroin doses (dose-response curve: 7.5, 15, 30, 60, and 100 mg/kg/injection). Specific disturbance of the endogenous opioid system was also apparent in the brain of adults with adolescent THC exposure. Striatal preproenkephalin mRNA expression was exclusively increased in the nucleus accumbens (NAc) shell; the relative elevation of preproenkephalin mRNA in the THC rats was maintained even after heroin self-administration. Moreover, m opioid receptor (mOR) GTP-coupling was potentiated in mesolimbic and nigrostriatal brainstem regions in THC-pretreated animals. mOR function in the NAc shell was specifically correlated to heroin intake. The current findings support the gateway hypothesis demonstrating that adolescence cannabis exposure has an enduring impact on hedonic processing resulting in enhanced opiate intake, possibly as a consequence of alterations in limbic opioid neuronal populations.

show abstract

“…Exposed rats exhibited decreased levels of D2 receptor expression and binding in the NAc, a key reward center, and increased sensitivity to the rewarding properties of opiates (DiNieri et al, 2011). Others have shown that exposure to THC during a period equivalent to midgestation in humans resulted in increased heroin-seeking behavior in offspring (Spano et al, 2007). Following a similar exposure paradigm, rats administered AMPH in adulthood were less sensitive to its locomotor-stimulating effects (Silva et al, 2012), indicative of aberrant responsiveness to psychostimulants.…”

Section: Cannabis/delta-9-tetrahydrocannabinolmentioning

confidence: 93%

Developmental Consequences of Fetal Exposure to Drugs: What We Know and What We Still Must Learn

Ross

Graham

Money

et al. 2014

Neuropsychopharmacol

342

241

View full text Add to dashboard Cite

Most drugs of abuse easily cross the placenta and can affect fetal brain development. In utero exposures to drugs thus can have long-lasting implications for brain structure and function. These effects on the developing nervous system, before homeostatic regulatory mechanisms are properly calibrated, often differ from their effects on mature systems. In this review, we describe current knowledge on how alcohol, nicotine, cocaine, amphetamine, Ecstasy, and opiates (among other drugs) produce alterations in neurodevelopmental trajectory. We focus both on animal models and available clinical and imaging data from cross-sectional and longitudinal human studies. Early studies of fetal exposures focused on classic teratological methods that are insufficient for revealing more subtle effects that are nevertheless very behaviorally relevant. Modern mechanistic approaches have informed us greatly as to how to potentially ameliorate the induced deficits in brain formation and function, but conclude that better delineation of sensitive periods, dose-response relationships, and long-term longitudinal studies assessing future risk of offspring to exhibit learning disabilities, mental health disorders, and limited neural adaptations are crucial to limit the societal impact of these exposures.

show abstract

Prenatal Cannabis Exposure Increases Heroin Seeking with Allostatic Changes in Limbic Enkephalin Systems in Adulthood

Cited by 136 publications

References 196 publications

Age-Dependent Effects of Cannabinoids on Neurophysiological, Emotional, and Motivational States

Age-Dependent Effects of Cannabinoids on Neurophysiological, Emotional, and Motivational States

Adolescent Cannabis Exposure Alters Opiate Intake and Opioid Limbic Neuronal Populations in Adult Rats

Developmental Consequences of Fetal Exposure to Drugs: What We Know and What We Still Must Learn

Contact Info

Product

Resources

About