Influence of the anabolic-androgenic steroid nandrolone on cannabinoid dependence

Area of Science:

• Neuropharmacology
• Addiction Science
• Behavioral Neuroscience

Background:

• Understanding factors contributing to drug addiction and motivational disorders is vital for public health.
• Anabolic-androgenic steroids (AAS) are frequently misused, and their interaction with other drugs of abuse is poorly understood.
• Delta-9-tetrahydrocannabinol (THC), the primary psychoactive compound in cannabis, has complex pharmacological and motivational effects.

Purpose of the Study:

• To investigate whether nandrolone exposure modifies the pharmacological and motivational effects of THC in a mouse model.
• To determine if nandrolone influences THC-induced conditioned place preference, tolerance development, and withdrawal symptoms.
• To assess the impact of nandrolone on THC's anxiolytic and anxiogenic-like effects.

Main Methods:

• Mice were treated with nandrolone via pre-exposure or co-administration before THC administration.
• Behavioral assays assessed antinociception, hypothermia, locomotion, conditioned place preference, anxiety-like behaviors, and THC withdrawal.
• Biochemical analyses examined CB1 receptor binding and G-protein activation in brain regions.

Main Results:

• Nandrolone did not alter the acute physical effects of THC or tolerance development.
• Nandrolone pre-exposure blocked THC- and food-induced conditioned place preference and exacerbated THC withdrawal symptoms.
• Nandrolone attenuated THC's anxiolytic-like effects but not its anxiogenic-like effects.

Conclusions:

• Chronic nandrolone treatment significantly alters behavioral responses associated with the addictive potential of THC.
• Nandrolone's effects on conditioned place preference and withdrawal suggest it may increase vulnerability to cannabis addiction.
• These findings highlight potential interactions between anabolic steroid use and cannabis's rewarding and aversive properties.