Sexually dimorphic alterations in locomotion and reversal learning after adolescent tetrahydrocannabinol exposure in the rat

Harte, Lauren; Dow-Edwards, Diana

doi:10.1016/j.ntt.2010.05.001

Cited by 48 publications

(44 citation statements)

References 53 publications

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“…As demonstrated by previous results [47], the locomotor system may be equally sensitive during THC administration in males and females at this age. In contrast, the sexually differential effects of THC during drug abstinence may be caused by greater CB1 receptor desensitization and down-regulation in the striatum and PFC of adolescent female rats compared to male rats after chronic THC administration [75;76], causing a potential decrease in CB1 receptor activation by endocannabinoids in female rats during drug abstinence.…”

Section: Discussionsupporting

confidence: 74%

“…The low dose of THC (2 mg/kg) was selected for use because this dose had previously been shown to produce effects on locomotor activity [47], but does not produce catalepsy, as is demonstrated by Wiley et al , [48]. Additionally, previous research conducted in our laboratory (see supplemental material) indicated peak plasma levels after a chronic dose of 2 mg/kg THC during adolescence to be 50–100 ng/mL in females, and 40–60 ng/mL in males.…”

Section: Methodsmentioning

confidence: 99%

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Withdrawal from THC during adolescence: Sex differences in locomotor activity and anxiety

Harte‐Hargrove

Dow-Edwards

2012

Behavioural Brain Research

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Research suggests that the use and abuse of marijuana can be especially harmful if it occurs during adolescence, a period of vast developmental changes throughout the brain. Due to the localization of cannabinoid receptors within the limbic system and the established effects of cannabinoids on emotional states and anxiety levels of rats and humans, we studied the sex- and dose-related effects of Δ9-tetrahydrocannabinol (THC, the main psychoactive component in marijuana) on behavior and anxiety during spontaneous withdrawal. Male and female Sprague Dawley rats were administered 2, 7.5 or 15 mg/kg THC or vehicle from postnatal day 35–41 (approximating mid-adolescence in humans). Locomotor activity and anxiety-related behaviors were measured during drug administration and abstinence. THC caused significant dose-dependent locomotor depression during drug administration. Locomotor depression initially abated upon drug cessation, but re-emerged by the end of the abstinence period and was greater in female than male rats. We found sensitization to the locomotor-depressing effects of THC in middle- and high-dose rats and the subsequent development of tolerance in high-dose rats. The high dose of THC increased anxiety-like behaviors while the low dose decreased anxiety-like behaviors during drug administration, with females more sensitive to the anxiogenic effects of THC than males. During abstinence, females were again especially sensitive to the anxiogenic effects of THC. This study demonstrates sexually-dimorphic effects of THC on anxiety-related behaviors and locomotor activity during and after THC administration during adolescence. This information may be useful in the development of therapeutic approaches for the treatment of marijuana withdrawal in adolescents.

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Section: Discussionsupporting

confidence: 74%

Section: Methodsmentioning

confidence: 99%

Withdrawal from THC during adolescence: Sex differences in locomotor activity and anxiety

Harte‐Hargrove

Dow-Edwards

2012

Behavioural Brain Research

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“…Researchers have typically used rodents to characterize the long-term effects of chronic cannabinoid administration during adolescence in both males and females (Biscaia et al, 2003;Rubino et al, 2008Rubino et al, , 2009Harte and Dow-Edwards, 2010;Llorente-Berzal et al, 2011;Mateos et al, 2011;Winsauer et al, 2011Winsauer et al, , 2012Harte-Hargrove and Dow-Edwards, 2012). Male rats that received D 9 -tetrahydrocannabinol (THC) during adolescence made more errors during the acquisition of a radial-arm maze task than males that received vehicle (Rubino et al, 2009).…”

Section: Introductionmentioning

confidence: 99%

Chronic 9-Tetrahydrocannabinol during Adolescence Differentially Modulates Striatal CB1 Receptor Expression and the Acute and Chronic Effects on Learning in Adult Rats

Weed

Filipeanu

Ketchum

et al. 2015

Journal of Pharmacology and Experimental Therapeutics

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The purpose of this study was to determine whether chronic administration of D 9-tetrahydrocannabinol (THC) during adolescence would (1) modify any sex-specific effects of THC on learning and (2) affect the development of tolerance to THC as an adult. Male and female rats received daily injections of saline or 5.6 mg/kg of THC from postnatal day 35-75, yielding four groups (female/saline, female/THC, male/saline, and male/THC). Rats were then trained on a procedure that assayed both learning and performance behavior and administered 0.32-18 mg/kg of THC acutely as adults (experiment 1). THC produced rate-decreasing and error-increasing effects in both sexes; however, female rats were more sensitive than male rats were to the rate-decreasing effects. Rats were then chronically administered 10 mg/kg of THC (experiment 2). Rats that received THC during adolescence developed tolerance to the rate-decreasing effects more slowly and less completely than did rats that received saline; in addition, females developed tolerance to the error-increasing effects of THC slower than males did. Western blot analysis of brain tissue indicated long-term changes in hippocampal and striatal cannabinoid type-1 receptor (CB1R) levels despite levels that were indistinguishable immediately after chronic treatment during adolescence. Striatal CB1R levels were increased in adult rats that received THC during adolescence; hippocampal CB1R levels varied by sex. In summary, female rats were more sensitive than male rats were to the acute and chronic effects of THC, and chronic administration of THC during adolescence produced long-term changes in CB1R levels that correlated with decreased tolerance development to the rate-decreasing effects of THC.

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“…Our results also indicate that in the object location task, only the females showed a significantly impaired performance in response to adolescent (pnd 28-43) cannabinoid exposure, suggesting that diverse aspects of memory function may be differentially affected in each sex [57]. Treatment Harte and Dow-Edwards [97] examined the effects of THC administered daily during juvenile or early adolescence (pnd [22][23][24][25][26][27][28][29][30][31][32][33][34][35][36][37][38][39][40] or late adolescence (pnd 41-60) on locomotor activity, development of tolerance, and acquisition/retention of spatial avoidance in adulthood. THC causes locomotor depression in both male and female animals treated during early adolescence but only in females treated during late adolescence.…”

Section: Cannabis and Psychiatric Disorders-a Focus On Schizophreniamentioning

confidence: 60%

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

Viveros

Marco

2015

Cannabinoid Modulation of Emotion, Memory, and Motivation

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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.

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Sexually dimorphic alterations in locomotion and reversal learning after adolescent tetrahydrocannabinol exposure in the rat

Cited by 48 publications

References 53 publications

Withdrawal from THC during adolescence: Sex differences in locomotor activity and anxiety

Withdrawal from THC during adolescence: Sex differences in locomotor activity and anxiety

Chronic 9-Tetrahydrocannabinol during Adolescence Differentially Modulates Striatal CB1 Receptor Expression and the Acute and Chronic Effects on Learning in Adult Rats

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

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