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

Harte‐Hargrove, Lauren C.; Dow-Edwards, Diana

doi:10.1016/j.bbr.2012.02.048

Cited by 61 publications

(46 citation statements)

References 117 publications

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“…Previous work in our laboratory has shown significant sex differences in both locomotor activity and anxiety (as measured by the elevated plus maze) during the drug abstinence period immediately following adolescent (P35–41) THC exposure [45]. Similarly treated animals also show deficits in reversal learning in the hippocampal-dependent active place avoidance task [23].…”

Section: Discussionmentioning

confidence: 99%

“…24 hours (P42) or 2 weeks following the last administration of THC (P56) rats were decapitated immediately following testing on the elevated plus maze [45] and brains were quickly removed and frozen in methylbutane (Fisher Scientific) kept at −20°C on dry ice, the methylbutane evaporated and the brains stored at −80°C. 20μM-thick coronal sections containing the dorsal hippocampus (according to [28]) were made on a Hacker cryostat microtome (3 sections/subject).…”

Section: Methodsmentioning

confidence: 99%

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Sex-specific alterations in hippocampal cannabinoid 1 receptor expression following adolescent delta-9-tetrahydrocannabinol treatment in the rat

Silva

Harte‐Hargrove

Izenwasser

et al. 2015

Neuroscience Letters

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Marijuana use by adolescents has been on the rise since the early 1990’s. With recent legalization and decriminalization acts passed, cannabinoid exposure in adolescents will undoubtedly increase. Human studies are limited in their ability to examine underlying changes in brain biochemistry making rodent models valuable. Studies in adult and adolescent animals show region and sex specific downregulation of the cannabinoid 1 (CB1) receptor following chronic cannabinoid treatment. However, although sex-dependent changes in behavior have been observed during the drug abstinence period following adolescent cannabinoid exposure, little is known about CB1 receptor expression during this critical time. In order to characterize CB1 receptor expression following chronic adolescent Δ-9-tetrahydrocannabinol (THC) exposure, we used [3H]CP55,940 binding to assess CB1 receptor expression in the dentate gyrus and areas CA1, CA2, and CA3 of the hippocampus in both male and female adolescent rats at both 24 hours and 2 weeks post chronic THC treatment. Consistent with other reported findings, we found downregulation of the CB1 receptor in the hippocampal formation at 24 hours post treatment. While this downregulation persisted in both sexes following two weeks of abstinence in the CA2 region, in females, this downregulation also persisted in areas CA1 and CA3. Expression in the dentate gyrus returned to the normal range by two weeks. These data suggest that selective regions of the hippocampus show persistent reductions in CB1 receptor expression and that these reductions are more widespread in female compared to male adolescents.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Sex-specific alterations in hippocampal cannabinoid 1 receptor expression following adolescent delta-9-tetrahydrocannabinol treatment in the rat

Silva

Harte‐Hargrove

Izenwasser

et al. 2015

Neuroscience Letters

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“…Anxiolytic effects were shown for low doses of the phytocannabinoid Δ 9 -tetrahydrocannabinol (THC; 0.075-2 mg/kg), the endocannabinoid anandamide (AEA; 0.1-1.25 mg/kg) and synthetic cannabinoids (WIN55,212-2: 0.5-3 mg/kg; CP55,940: < 0.1 mg/kg; HU210: 0.01 mg/kg) [21,43,53,65,67,68,[75][76][77][78][79][80][81][82][83][84][85][86][87][88][89][90]. Higher doses of the same agonists (THC: 2.5-10 mg/ kg; AEA: 10 mg/kg; WIN55,212-2: 3-5 mg/kg; CP55,940: > 0.1 mg/kg; HU210: 0.05-0.1 mg/kg) were anxiogenic [40,44,71,78,83,[89][90][91][92][93][94][95][96][97][98][99][100][101][102][103][104]. High doses of THC increased anxiety in humans as well [105][106][107][108]…”

Section: Increased Endocannabinoid Activitymentioning

confidence: 99%

Interactions Between Cannabinoid Signaling and Anxiety: A Comparative Analysis of Intervention Tools and Behavioral Effects

Aliczki

Haller

2015

Cannabinoid Modulation of Emotion, Memory, and Motivation

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Cannabinoid signaling is believed to decrease anxiety, albeit the conflicting nature of evidence is generally acknowledged. Here we provide a comprehensive overview of available findings by grouping them according to the tools that have been used to modulate cannabinoid signaling. The systemic administration of cannabinoid receptor agonists and antagonists led to the most conflicting findings; such treatments may increase, decrease, or leave anxiety unaffected. In addition, antagonists and agonists had similar effects in many instances including their biphasic effects. The effects of genetic manipulations, cannabinoid synthesis or reuptake inhibition as well as the effects of local brain treatments with cannabinoid ligands appear more consistent. We suggest that systemically administered receptor ligands affect cannabinoid signaling globally and as such lack the spatial and temporal specificity of endocannabinoid signaling. By contrast, gene disruption and the indirect modulation of endocannabinoid availability affect ongoing (natural) processes and lead to more specific and consistent effects. Local brain treatments whit receptor ligands are spatially restricted which increases the consistency of findings, but also reveals that cannabinoids affect anxiety in a brain area-specific manner, which further explains the inconsistency of findings with systemically injected ligands. Environmental conditions have a large impact on effects with all techniques, suggesting that endocannabinoid signaling affects coping with environmental challenges rather than unconditionally decreasing anxiety. The relationship between cannabinoid signaling, anxiety and coping styles is largely understudied, but holds great promise for understanding the roles of cannabinoids in behavioral control and may broaden their therapeutic implications.

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“…Females are more sensitive than males to the reinforcing, anxiogenic, spatial memory-impairing, hypothermic, antinociceptive and sedative effects of cannabinoids (Cha et al, 2007; Craft et al, 2012; Fattore et al, 2007; Harte-Hargrove and Dow-Edwards, 2012; Romero et al, 2002; Tseng and Craft, 2001). For example, i.p.…”

Section: Introductionmentioning

confidence: 99%

Sex differences in antinociceptive tolerance to delta-9-tetrahydrocannabinol in the rat

Wakley

Wiley

Craft

2014

Drug and Alcohol Dependence

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Background Sex differences in cannabinoid effects have been reported in rodents, with adult females typically being more sensitive than adult males. The present study compared the development of antinociceptive tolerance to delta-9-tetrahydrocannabinol (THC) in adult, gonadally intact female vs. male rats. Methods Cumulative dose-effect curves were obtained for THC (1.0–18 mg/kg i.p.) on warm water tail withdrawal and paw pressure tests. Vehicle or the sex-specific ED80 dose for THC was administered twice daily for 9 days; THC dose-effect curves were then re-determined. Results On the pre-chronic test day, THC was significantly more potent in females than males in producing antinociception on the tail withdrawal and paw pressure tests. After 9 days of twice-daily THC treatment (5.4 mg/kg/injection in females, 7.6 mg/kg/injection in males), THC potency on both tests decreased more in females than males. On the tail withdrawal test, chronic THC produced 4.2- vs. 2.8-fold increases in ED50 values in females vs. males, respectively. On the paw pressure test, chronic THC produced 4.4- vs. 2.9-fold increases in ED50 values in females vs. males, respectively. Chronic THC treatment did not significantly disrupt estrous cycling in females. Conclusions These results demonstrate that – even when sex differences in acute THC potency are controlled for – females develop more antinociceptive tolerance to THC than males. Given the importance of drug tolerance in the development of drug dependence, these results suggest that females may be more vulnerable than males to developing dependence after chronic cannabinoid exposure.

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

Cited by 61 publications

References 117 publications

Sex-specific alterations in hippocampal cannabinoid 1 receptor expression following adolescent delta-9-tetrahydrocannabinol treatment in the rat

Sex-specific alterations in hippocampal cannabinoid 1 receptor expression following adolescent delta-9-tetrahydrocannabinol treatment in the rat

Interactions Between Cannabinoid Signaling and Anxiety: A Comparative Analysis of Intervention Tools and Behavioral Effects

Sex differences in antinociceptive tolerance to delta-9-tetrahydrocannabinol in the rat

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