Long-term behavioral effects of perinatal exposure to Δ9-tetrahydrocannabinol in rats: Possible role of pituitaryadrenal axis

Rubio, Pilar; Fonseca, Fernando Rodrı́guez de; Muñoz, Riansares; Ariznavarreta, C.; Martı́n-Calderón, Jose Luis; Navarro, Miguel

doi:10.1016/0024-3205(95)00204-j

Cited by 69 publications

(60 citation statements)

References 19 publications

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“…An alternative explanation would point to changes in general locomotor activity that could have been induced by the treatment in the females; these motor alterations could result in an elevated frequency of exploratory behavior (and therefore higher chances of pressing the lever during the acquisition phase). In this sense, it has been shown that female rats perinatally exposed to THC showed persistent changes in spontaneous locomotor activity (Navarro et al, 1994;Rubio et al, 1995). Additionally adult rats treated with the CB1 agonist WIN exhibited an increased locomotor activity as measured in the open field, but only at the lowest dose tested (0.6 mg/kg) .…”

Section: Adolescent Cannabis and Adult Cocaine Addictionmentioning

confidence: 98%

Augmented Acquisition of Cocaine Self-Administration and Altered Brain Glucose Metabolism in Adult Female but not Male Rats Exposed to a Cannabinoid Agonist during Adolescence

Higuera-Matas

Soto-Montenegro

Olmo

et al. 2007

Neuropsychopharmacol

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Marijuana consumption during adolescence has been proposed to be a stepping-stone for adult cocaine addiction. However, experimental evidence for this hypothesis is missing. In this work we chronically injected male and female Wistar rats with either the cannabinoid agonist CP 55,940 (CP; 0.4 mg/kg) or its corresponding vehicle. Adult acquisition (seven 30 min daily sessions) and maintenance (fourteen 2 h daily sessions) of cocaine self-administration (1 mg/kg), food-reinforced operant learning under conditions of normal (ad libitum access to food), and high motivation (food-restriction schedule) were measured. Additionally, brain metabolic activity was analyzed by means of [ 18 F]-fluorodeoxyglucose positron emission tomography. During the acquisition phase, female CP-treated rats showed a higher rate of cocaine self-administration as compared to vehicle-treated females and males; no differences were found between both male groups. This effect disappeared in the maintenance phase. Moreover, no differences among groups were evident in the food-reinforced operant task, pointing to the cocaine-specific nature of the effect seen in self-administration rather than a general change in reward processing. Basal brain metabolic activity also changed in CP-treated females when compared to their vehicle-treated counterparts with no differences being found in the males; more specifically we observed a hyper activation of the frontal cortex and a hypo activation of the amygdalo-entorhinal cortex. Our results suggest that a chronic exposure to cannabinoids during adolescence alters the susceptibility to acquire cocaine self-administration, in a sex-specific fashion. This increased susceptibility could be related to the changes in brain metabolic activity induced by cannabinoids during adolescence.

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Section: Adolescent Cannabis and Adult Cocaine Addictionmentioning

confidence: 98%

Augmented Acquisition of Cocaine Self-Administration and Altered Brain Glucose Metabolism in Adult Female but not Male Rats Exposed to a Cannabinoid Agonist during Adolescence

Higuera-Matas

Soto-Montenegro

Olmo

et al. 2007

Neuropsychopharmacol

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“…As described aboye, matemal exposuro tu cannabinoids not only results in developmontal a¡terations uf [he dopaminergic systems in Ihe brain (Bonnin el al., 1994;Rodríguez do Fonseca el al., 1990, 1991a, 1992a, but lii permanení neuro-chemical alteratjoas in adulthoud (García ot al. 1996;Navarro, de Miguel, Rodríguez de Fonseca, Ramos, & Fernández-Ruiz, 1996;Navarro, Rodríguez de Fonseca, Hernández, Ramos, & Fernández-Ruiz, 1994a;Navarro, Rubio, & Rodríguez de Fonseca, 1995;Rubio el al., ¡995). lf we considor theso observatiuns íogether wilh the data reflecting the alíeratiuns in the bohaviural reactivity tu novelty and the response tu morphine, as well as tho UPA a¡lorations, we can argue that maternal exposure tu '[HG leads tu a vulnerable phenotype, partially resembling thaI proposed fui amphotamine solfadministration : mesucorticolimbic dupaminorgic altorations, increasod behaviural responses tu nuvelty, and a sharp adrencil response tu adaptivo challengos (Piazza et al, 1959(Piazza et al, , 1993(Piazza et al, , 1996.…”

Section: Discussionmentioning

confidence: 99%

“…Several studies have shown that maternal exposure to opiates (Gagin, Kook, Cohen, & Savil, 1997) or to psychostirnulants (Keller,Lefevre,Raucci,Caríson,& Glick,¡996) (Molina, Wagner, & Spear, 1994;Rubio et al, 1995). The effects of such epigenetic intIuences in brain reward systems bave been studied by the exíensive research of Piazza's group ( Piazza, Deminiere, Le Moal, & Simon, 1989;Piazza, Deroche, Derniniére, Maccari, Le Moal, & Simon, 1993;Piazza & Le Moal, 1996).…”

mentioning

confidence: 99%

“…Subsequent studies developed in our laboratory (Table 1, references in section E) revealed that maternal exposure to cannabinoids resulted in behavioral alterations which could be observed either during development or at adult ages. Ihese alterations were associated with neurochemical disturbances in nionoaminergic and neuro-pepúde systems (Bonnin et al, 1994;Molina-Holgado et al, 1993;Rubio et al, 1995).…”

mentioning

confidence: 99%

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Early Cannabinoid Exposure as a Source of Vulnerability to Opiate Addiction: A Model in Laboratory Rodents

Navarro

Fonseca

1998

Span. J. Psychol.

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Recent findings have identified an endogcnous brain system mediating ihe actions of cannab/s sol/ro preparations. This system includes Ihe brain cannabinoid receptor (GB-1) and iís endogenous ligands anandamide aud 2-arachidonoyl-glycerol. The endogenous cannabinoid system is not only present in the adult brain, huí is also active at early stages of brain development. Studies developed at our laboratory have revealed thai maternal exposure to psychoactive cannabinoid resulis in neuro-developmental alterations. A model is proposed in which early A 9-tetrahydrocannabinol (THC) exposure during critical dcvclopmental periods results in permanení alterations in brain fuoction by either the stimulation of CB-I receptors present during the development, or by the alterations in maternal glucocorticoid secrerion. Thosc alterations will be revealed in adulthood afíer challenges either with drogs (le. opiates) or with environmental stressors (le. nove]ty). They wfll include a modifled patrera of neuro-chemical, endocdne, and behavioral responses that might lead ultimately lo inadaptation and vulnerability to opiate abuse. K~.y vvords: mt, cannobino/ds, perinatal exposure, /,ehav/or op/ates, condit/oning, A CTH, corticosterone, vulnerabitiiyEn los ultimos años se ha logrado identificar un sistema endógeno que media las acciones de los principios activos del cannabis sativa. Este sistema está compuesto por el receptor para cannabinoides cerebral (CB-1>, y sus ligandos endógenos, la anandamida y el 2-araquídonilglicerol. El sistema cannabinoide endógeno está activo en el cerebro adulto, participando también en el desarrollo cerebral. Los estudios desarrollados en nuestro laboratorio han demostrado que la exposición maternal durante la gestación y la lactancia a compuestos activos en el receptor CB-1 conducen a alteraciones en el desarrollo cerebral. En este trabajo se propone un modelo en el cual la exposición durante periodos críticos del desarrollo a J9-tetrahydrocannabinol (THC), el principal cannabinoide psicoactivo del cannabis sativa, induce cambios permanentes en la función cerebral, bien mediante la activación de los receptores CB-1 presentes durante edades tempranas del desarrollo, o bien mediante la alteración de la secreción maternal de glucocorticoides. Estas alteraciones se manifiestan en la edad adulta tras la exposición a desafíos adaptativos, como el tratamiento con drogas de abuso (opiáceos> o el estrés medioambiental (novedad, etc.), que inducen respuestas neuroquimicashormonales y comportamentales anómalas, que se manifiestan como una mayor vulnerabilidad a la adicción.

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“…In this same study, rats showed deficits in social behaviors during adolescence and elevated anxiety in adulthood. Increased locomotor activity has been demonstrated as well (Borgen et al, 1971;Mereu et al, 2003;Rubio et al, 1995), although others have shown either no changes in locomotion or significant hypoactivity (for review, see Navarro et al (1995);Schneider (2009)). …”

Section: Cannabis/delta-9-tetrahydrocannabinolmentioning

confidence: 99%

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

Ross

Graham

Money

et al. 2014

Neuropsychopharmacol

327

241

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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.

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Long-term behavioral effects of perinatal exposure to Δ9-tetrahydrocannabinol in rats: Possible role of pituitaryadrenal axis

Cited by 69 publications

References 19 publications

Augmented Acquisition of Cocaine Self-Administration and Altered Brain Glucose Metabolism in Adult Female but not Male Rats Exposed to a Cannabinoid Agonist during Adolescence

Augmented Acquisition of Cocaine Self-Administration and Altered Brain Glucose Metabolism in Adult Female but not Male Rats Exposed to a Cannabinoid Agonist during Adolescence

Early Cannabinoid Exposure as a Source of Vulnerability to Opiate Addiction: A Model in Laboratory Rodents

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

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