Graptophyllum grandulosum Prevents Nicotine Addiction in Pubescent Adolescent Rats: Evidence on Dopaminergic, Cholinergic, BDNF and Neuroinflammatory Pathways.

Graptophyllum grandulosum (G. grandulosum) is a plant of the Acanthaceae family found in the Littoral region of Cameroon. This plant is traditionally used by the local population for its various medicinal properties. G. grandulosum contains multiple bioactive compounds such as chrysoeriol and luteolin. This study aimed to evaluate the preventive effect of the aqueous extract of G. grandulosum on nicotine-induced addiction. 42 Wistar pubescent adolescent male rats were used during this experiment. Nicotine addiction was induced following a 5 days injections of nicotine tartrate (0.4 mg/kg, sc). The behavioural assessment was done using the Conditioned Place Preference (CPP) test and the Elevated plus maze (EPM) test. 24 h following the last nicotine administration, animals were evaluated for preference change in the CPP and 1 h following this test, animals were submitted to the EMP. The animals were sacrificed; the hippocampus and striatum were collected for biochemicals assays (dopamine, acetylcholine, Brain-Derived Neurotrophic Factor (BDNF) and proinflammatory cytokines). The acute toxicity of G. grandulosum was also performed. G. grandulosum prevented CPP preference change (p < 0.001) induced by nicotine injection and reduced hyperactivity and risk taking (p < 0.001) in the EPM test. G. grandulosum reduced dopamine levels (p < 0.001) and increased acetylcholine levels (p < 0.01). Additionally, G. grandulosum modulated BDNF levels (p < 0.001) and reduced proinflammatory cytokines (Interleukine-1β (IL-1β) and Tumor necrosis factor (TNFα)) (p < 0.01). G. grandulosum did not present any sign of toxicity. These results suggest that G. grandulosum prevents addictive behavior via the modulation of dopaminergic, cholinergic, BDNF and neuroinflammatory pathways.