Background: Attention Deficit Hyperactivity Disorder (ADHD) can be comorbid with depression, often leading to prescription of both methylphenidate (MP) and selective serotonin reuptake inhibitor (SSRI) antidepressants, such as fluoxetine (FLX). Moreover, these drugs are often misused as a cognitive enhancer. This study examined the effects of chronic oral co-administration of MP and FLX on depressive- and anxiety-like behaviors. Methods: Adolescent rats received daily either water (control), MP, FLX, or the combination of MP plus FLX in their drinking water over the course of 4 weeks. Results: Data analysis show a decrease in food consumption and body weight for rats exposed to FLX or the combination of MP and FLX. Sucrose consumption was significantly greater in FLX or MP+FLX groups as compared to controls. FLX treated rats showed no effect in the elevated plus maze (EPM; open arm time) and forced swim test (FST; latency to immobility). However, rats treated with the combination (MP+FLX) showed significant anxiolytic-like and anti-depressive-like behaviors (as measured by EPM and FST), as well as significant increases in overall activity (distance traveled in open field test). Finally, the combined MP+FLX treatment induced a decrease in anxiety and depressive-like behaviors that was significantly greater than the response from either of these two drugs alone. Conclusion: These behavioral results characterize the long-term effects of these drugs (orally administered) that are widely co-administered and co-misused and provide important insight into the potential neurobiological and neurochemical effects. Future research will determine the potential risks of the long-term use of MP and FLX together.

Background: Delta-9-tetrahydrocannabinol (THC) is the main psychoactive component of cannabis. Historically, rodent studies examining the effects of THC have used intraperitoneal injection as the route of administration, heavily focusing on male subjects. However, human cannabis use is often through inhalation rather than injection. Objective: We sought to characterize the pharmacokinetic and phenotypic profile of acutely inhaled THC in female rats, compared to intraperitoneal injection, to identify any differences in exposure of THC between routes of administration. Methods: Adult female rats were administered THC via inhalation or intraperitoneal injection. Serum samples from multiple time points were analyzed for THC and metabolites 11-hydroxy-delta-9-tetrahydrocannabinol and 11-nor-9-carboxy-delta-9-tetrahydrocannabinol using ultra-performance liquid chromatography-tandem mass spectrometry. Rats were similarly treated for locomotor activity analysis. Results: Rats treated with 2 mg/kg THC intraperitoneally reached a maximum serum THC concentration of 107.7 ± 21.9 ng/mL. Multiple THC inhalation doses were also examined (0.25 mL of 40 or 160 mg/mL THC), achieving maximum concentrations of 43.3 ± 7.2 and 71.6 ± 22.5 ng/mL THC in serum, respectively. Significantly reduced vertical locomotor activity was observed in the lower inhaled dose of THC and the intraperitoneal injected THC dose compared to vehicle treatment. Conclusion: This study established a simple rodent model of inhaled THC, demonstrating the pharmacokinetic and locomotor profile of acute THC inhalation, compared to an i.p. injected THC dose in female subjects. These results will help support future inhalation THC rat research which is especially important when researching behavior and neurochemical effects of inhaled THC as a model of human cannabis use.

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Objective: Research points to exercise having a positive effect in fighting relapse and use of drugs of abuse. Through conducting this research, differences have been observed in the effects of exercise on drug abuse between sexes. Many of the studies found that exercise tends to cause a more profound effect in blocking drug relapse or reinstatement in males when compared with females.Methods: Our hypothesis is that these differences in response to drugs of abuse after an exercise regimen could in part be attributed to variations in testosterone levels between males and females.Results: Testosterone has been shown to have a modulatory impact on the dopaminergic activity in the brain, causing an effect on the brain's response to drugs of abuse. Exercise has demonstrated a causal effect on increasing testosterone levels in males, whereas drugs of abuse decrease testosterone levels in males.Conclusions: Thus, exercise raising testosterone levels in males helps to decrease the dopaminergic response in the brain to drugs of abuse causing attenuation to drugs. To find sex-specific exercise treatments for drugs of abuse, it is important to continue researching exercise's efficacy against drugs of abuse.