Locomotor activity changes in female adolescent and adult rats during repeated treatment with a cannabinoid or club drug

Abstract

Adolescents and young adults of both sexes are the primary consumers of "club" drugs; yet, most of the mechanistic preclinical research in this area has been performed in adult male rodents. The purpose of this study was to evaluate the acute and repeated effects of drugs that are commonly abused by adolescents in female adolescent and adult rats in a rodent model of behavioral sensitization. During two five-day periods separated by a two-day break, rats were injected daily with saline or with one of the following drugs: cocaine (7 or 15 mg/kg), ketamine (3 or 10 mg/kg), 3,4-methylenedioxymethamphetamine (MDMA) (3, 10, or 30 mg/kg), or Δ(9)-tetrahydrocannabinol (THC) (0.03, 0.1, 0.3 or 1 mg/kg) and their locomotor activity was measured. Cocaine increased activity across days in both age groups. Whereas ketamine produced progressive increases in activity with repeated administration in rats of both ages, MDMA increased, and then decreased, activity in the chronic dosing regimen in female adolescents only. Tolerance to the initial stimulatory effects of low doses of THC was observed at both ages. The results with THC are similar to those obtained for male rats tested under identical conditions in a previous study; however, in contrast with the present results in females, male adolescent rats in the previous study failed to develop behavioral sensitization to ketamine. Together, these results suggest that age and sex strongly influence the progressive adaptive changes that occur with repeated administration of some, but not all, of these commonly abused substances.

Locomotor sensitization to intermittent ketamine administration is associated with nucleus accumbens plasticity in male and female rats

“…In male rats, ketamine-induced locomotor sensitization has been observed in doses as low as 5 mg/kg and as high as 50 mg/kg (Popik et al , 2008; Botanas et al , 2015). Additionally, one study reported locomotor sensitization at a dose of 10 mg/kg in female rats (Wiley et al , 2011). The present study demonstrates that repeated, intermittent ketamine administration at a dose of 5 mg/kg, but not 2.5 mg/kg, produces behavioral sensitization in male rats.…”

“…Upstream signaling molecules such as brain-derived neurotrophic factor (BDNF) can influence downstream signaling targets such as ΔfosB, a transcription factor heavily associated with addiction (Wiley et al , 2011; Li and Wolf, 2015). Thus, the present study sought to examine whether protein expression of the aforementioned targets could be affected by low-dose ketamine as they are affected by other drugs of abuse like cocaine.…”

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

“…The few exceptions were all from the same lab (Wiley, 2003; Wiley et al, 2011, 2007). In the first study (Wiley, 2003), female mice were more sensitive than males to acute THC-induced hyperlocomotion; after 2.5 days of twice-daily THC injections, only females showed dose-dependent changes in THC’s effect.…”

Investigation of sex-dependent effects of cannabis in daily cannabis smokers

“…This research was supported by US National Institute on Drug Abuse Grant DA19239, DA09236, and DA02775. The authors acknowledge and appreciate the exceptional assistance of Divya Lakhaney, Elyssa Berg, Michael Harakas, Sarah Badach, Bennett Wechsler, and Ursula Rogers in data collection.…”