Effects of acute cannabidiol on behavior and the endocannabinoid system in HIV-1 Tat transgenic female and male mice

Abstract

BackgroundSome evidence suggests that cannabidiol (CBD) has potential to help alleviate HIV symptoms due to its antioxidant and anti-inflammatory properties. Here we examined acute CBD effects on various behaviors and the endocannabinoid system in HIV Tat transgenic mice.MethodsTat transgenic mice (female/male) were injected with CBD (3, 10, 30 mg/kg) and assessed for antinociception, activity, coordination, anxiety-like behavior, and recognition memory. Brains were taken to quantify endocannabinoids, cannabinoid receptors, and cannabinoid catabolic enzymes. Additionally, CBD and metabolite 7-hydroxy-CBD were quantified in the plasma and cortex.ResultsTat decreased supraspinal-related nociception and locomotion. CBD and sex had little to no effects on any of the behavioral measures. For the endocannabinoid system male sex was associated with elevated concentration of the proinflammatory metabolite arachidonic acid in various CNS regions, including the cerebellum that also showed higher FAAH expression levels for Tat(+) males. GPR55 expression levels in the striatum and cerebellum were higher for females compared to males. CBD metabolism was altered by sex and Tat expression.ConclusionFindings indicate that acute CBD effects are not altered by HIV Tat, and acute CBD has no to minimal effects on behavior and the endocannabinoid system.

Cannabinoid receptor 1 positive allosteric modulator ZCZ011 shows differential effects on behavior and the endocannabinoid system in HIV-1 Tat transgenic female and male mice

“…In the present study, sex-dpendent alterations were noted for AEA, PEA, OEA, and AA levels in the striatum. Similar to previous study [108], the current study displayed higher AA levels in males compared to females in the prefrontal cortex and striatum, which is not surprising as males also displayed higher levels of AEA, OEA, and PEA, which are metabolized into AA. Moreover, even though CB 1 R and CB 2 R expression was not affected by Tat, females demonstrated higher levels of cannabinoid receptors (CB 1 R and CB 2 R) in prefrontal cortex, striatum, and cerebellum whereas males displayed higher levels of degradative enzymes (FAAH and MAGL).…”

“…A potential mechanism by which GAT211 reduced the MK801-induced hyperlocomotion is by inhibiting CB 1 Rs on dysregulated glutamatergic and GABAergic neurons that are involved with modulating motor activity in the cortico-striatal-limbic circuitry responsible for hyperarousal [76, 77]. These data suggest that CB 1 R PAMs can potentially normalize locomotor activity in diseased states, making them an attractive target for treating locomotor activity-related deficits, even though several studies have shown Tat-induced hypolocomotion [78, 79, 80]. The lack of Tat effects on locomotor activity may be related to immune tolerance seen with prolonged Tat exposure [81].…”

Cannabinoid receptor 1 positive allosteric modulator ZCZ011 shows differential effects on behavior and the endocannabinoid system in HIV-1 Tat transgenic female and male mice

“…In the present study, sex-dpendent alterations were noted for AEA, PEA, OEA, and AA levels in the striatum. Similar to previous study [ 111 ], the current study displayed higher AA levels in males compared to females in the prefrontal cortex and striatum, which is not surprising as males also displayed higher levels of AEA, OEA, and PEA, which are metabolized into AA. Moreover, even though CB 1 R and CB 2 R expression was not affected by Tat, females demonstrated higher levels of cannabinoid receptors (CB 1 R and CB 2 R) in prefrontal cortex, striatum, and cerebellum whereas males displayed higher levels of degradative enzymes (FAAH and MAGL).…”

“…A potential mechanism by which GAT211 reduced the MK801-induced hyperlocomotion is by inhibiting CB 1 Rs on dysregulated glutamatergic and GABAergic neurons that are involved with modulating motor activity in the cortico-striatal-limbic circuitry responsible for hyperarousal [81,82]. These data suggest that CB 1 R PAMs can potentially normalize locomotor activity in diseased states, making them an attractive target for treating locomotor activity-related deficits, even though several studies have shown Tat-induced hypolocomotion [83][84][85]. The lack of Tat effects on locomotor activity may be related to immune tolerance seen with prolonged Tat exposure [86].…”