Supraadditive effect of d-fenfluramine plus phentermine on extracellular acetylcholine in the nucleus accumbens: possible mechanism for inhibition of excessive feeding and drug abuse.

The combination of d-fenfluramine plus phentermine (d-FEN/PHEN) provides a tool for exploring neural mechanisms that control food intake and drug abuse. Prior research suggests that dopamine (DA) in the nucleus accumbens can reinforce appetitive behavior and acetylcholine (ACh) inhibits it. When rats were given d-fenfluramine (5 mg/kg, IP) DA increased to 169% (p < 0.01), and ACh decreased slightly. Phentermine (5 mg/kg, IP) increased extracellular DA to 469% of baseline and ACh increased slightly to 124% (both p < 0.01). The d-FEN/PHEN combination, however, increased both DA and ACh with a supraadditive effect on ACh to 172%. One interpretation is that dFEN/PHEN increases DA like a meal or drug of abuse, while also increasing ACh to stop further approach behavior. This leaves the animal "satiated," as defined by reduced intake of food or drugs.