Continuous amphetamine and cocaine have similar neurotoxic effects in lateral habenular nucleus and fasciculus retroflexus.

Both amphetamine and cocaine lead to an intake pattern in chronic addicts in which the drug is taken repeatedly over prolonged periods. While continuously administered amphetamines, designed to mimic this intake pattern, have a neurotoxic effect on caudate dopamine terminals, several studies have failed to find similar effects following continuous cocaine. In this study, these findings in striatum were replicated in rats using silver staining for degenerating neurons. But it was further found that either amphetamine or cocaine given continuously over a 3- to 5-day period induce a highly specific pattern of axonal degeneration extending from the lateral habenular nucleus along the fasciculus retroflexus towards the ventral tegmentum. This finding supports a rich literature on the involvement of these same pathways in the actions of dopamine agonists, reward mechanisms, and the integration of limbic, extrapyramidal, and midbrain centers.