A compound called 2,5-dimethoxy-4-propylamphetamine (DOPR), a psychedelic that activates 5-HT2A receptors, can increase motivation in mice with low baseline motivation without causing hallucinogenic-like effects. In a progressive ratio breakpoint task (PRBT) involving 80 mice, doses as low as 0.0106 mg/kg improved performance only in animals with low initial motivation; high-performing mice were unaffected. The head-twitch response (HTR) assay in 72 mice showed hallucinogenic-like effects only at doses of 0.1 mg/kg or higher. These results suggest that low doses of DOPR might treat amotivated states while avoiding hallucinogenic side effects, warranting further research in rodents with disease-relevant conditions.
Delta-9-tetrahydrocannabinol (THC), the main psychoactive component of cannabis, reduced pain sensitivity, body temperature, and movement in HIV-1 transgenic rats and their controls, with some differences between males and females. A higher dose (3 mg/kg) also temporarily lowered motivation to work for a reward, but this effect disappeared after 16 days of daily treatment. HIV-1 transgenic rats showed lower motivation than one control strain (Fischer344) but not another (wildtype littermates), highlighting the importance of choosing appropriate control groups in research.
In a rat model of HIV, the psychoactive component of cannabis, THC, had opposite effects on different cognitive functions: it improved learning but worsened risk-based decision-making. HIV-transgenic rats and controls were tested on two tasks before and after acute and chronic THC injections. At baseline, HIV rats showed slower decision-making but intact cognition, suggesting early deficits. THC selectively altered performance in HIV rats, enhancing learning while impairing decision-making, effects not seen in controls. These findings mirror function-dependent cannabis effects observed in people with HIV and suggest THC may drive cannabis-induced cognitive changes in this population.
People with HIV often develop cognitive problems linked to disrupted fronto-striatal brain circuits, which are also affected by cannabis. HIV transgenic rats, which model HIV-associated neurocognitive disorder, showed a significant prepulse inhibition deficit compared to healthy controls, mirroring the sensorimotor gating impairment seen in people with HIV. Acute treatment with THC (1 and 3 mg/kg) reduced prepulse inhibition in control rats but not in HIV transgenic rats, indicating a relative insensitivity to THC's disruptive effects on fronto-striatal function. Cannabidiol (1, 10, and 30 mg/kg) had only minor, genotype-independent effects on prepulse inhibition. This reduced sensitivity may help explain higher cannabis use rates among people with HIV.