Amphetamine and pseudoephedrine cross-tolerance measured by c-Fos protein expression in brains of chronically treated rats

Background: Pseudoephedrine is a drug commonly prescribed as a nasal decongestant and
bronchodilator and is also freely available in cold remedies and medications. The structural and
pharmacological similarity of pseudoephedrine to amphetamine has led to evaluation of its
psychomotor stimulant properties within the central nervous system. Previous investigations have
shown that the acute responses to pseudoephedrine were similar to those of amphetamine and
other psychostimulants.
Results: This study examined the effect of chronic administration of pseudoephedrine in rat
nucleus accumbens and striatum and identified three further similarities to amphetamine. (i)
Chronic exposure to pseudoephedrine reduced the c-Fos response to acute pseudoephedrine
treatment suggesting that pseudoephedrine induced tolerance in the animals. (ii) In animals
chronically treated with amphetamine or pseudoephedrine the acute c-Fos response to
pseudoephedrine and amphetamine was reduced respectively as compared to naïve animals
indicating cross-tolerance for the two drugs. (iii)The known involvement of the dopamine system
in the response to amphetamine and pseudoephedrine was further confirmed in this study by
demonstrating that pseudoephedrine similarly to amphetamine, but with lower potency, inhibited
[3H]dopamine uptake in synaptosomal preparations.
Conclusion: This work has demonstrated further similarities of the effect of pseudoephedrine to
those of amphetamine in brain areas known to be associated with drug addiction. The most
significant result presented here is the cross tolerance effect of amphetamine and psudoephedrine.
This suggests that both drugs induce similar mechanisms of action in the brain. Further studies are
required to establish whether despite its considerable lower potency, pseudoephedrine could pose
health and addiction risks in humans similar to that of known psychostimulants.

Citation:
Ruksee, N. et al. (2008) ‘Amphetamine and pseudoephedrine crosstolerance measured by c-Fos protein expression in brains of chronically treated rats’ BMC Neuroscience, 9 (99).