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

Ruksee N, Tongjaroenbuangam W, Casalotti SO, Govitrapong P - BMC Neurosci (2008)

Bottom Line: 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.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 pseudoephedrine.

View Article: PubMed Central - HTML - PubMed

Affiliation: Neuro-Behavioral Biology Center, Institute of Science and Technology, Research and Development, Mahidol University, Salaya, Nakornpathom, 73170, Thailand. cfncn@mahidol.ac.th

ABSTRACT

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 pseudoephedrine. 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.

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[3H]dopamine uptake in rat brain synaptosomes. Effect of d-amphetamine and d-pseudoephedrine on [3H]dopamine uptake in rat striatal (n = 8) and nucleus accumbens (n = 4) synaptosomes. IC50 is defined as the concentration of drug producing a 50 percent inhibition in 1 nM [3H]dopamine uptake. Values represent uptake as percentage of control. IC50 values are mean ± S.E.M. from duplicate samples in each independent experiment. The IC50 values of amphetamine in inhibiting [3H]dopamine uptake in striatum and nucleus accumbens are 4.28 ± 0.47 and 2.95 ± 0.42 μM, respectively, and of d-pseudoephedrine in inhibiting [3H]dopamine uptake in striatum and nucleus accumbens are 667 ± 126 and 530 ± 61 μM, respectively.
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Figure 4: [3H]dopamine uptake in rat brain synaptosomes. Effect of d-amphetamine and d-pseudoephedrine on [3H]dopamine uptake in rat striatal (n = 8) and nucleus accumbens (n = 4) synaptosomes. IC50 is defined as the concentration of drug producing a 50 percent inhibition in 1 nM [3H]dopamine uptake. Values represent uptake as percentage of control. IC50 values are mean ± S.E.M. from duplicate samples in each independent experiment. The IC50 values of amphetamine in inhibiting [3H]dopamine uptake in striatum and nucleus accumbens are 4.28 ± 0.47 and 2.95 ± 0.42 μM, respectively, and of d-pseudoephedrine in inhibiting [3H]dopamine uptake in striatum and nucleus accumbens are 667 ± 126 and 530 ± 61 μM, respectively.

Mentions: In order to investigate the mechanism of action of pseudoephedrine and to compare it to that of amphetamine, the effect of pseudoephedrine and amphetamine on [3H]dopamine uptake was assayed in synaptosomal preparations from rat brain areas. Both amphetamine and pseudoephedrine inhibited the uptake of [3H]dopamine into nucleus accumbens and striatal synaptosomes, with amphetamine being more potent than pseudoephedrine (Fig. 4). The amphetamine and pseudoephedrine curves were parallel to each other with the curve for pseudoephedrine inhibition of [3H]dopamine uptake shifted to the right. The IC50 values for amphetamine and pseudoephedrine inhibition reported here (see legend Fig. 4) indicate that amphetamine was 156 and 180 times more potent than pseudoephedrine at inhibiting [3H]dopamine uptake into striatal and nucleus accumbens synaptosomes, respectively.


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

Ruksee N, Tongjaroenbuangam W, Casalotti SO, Govitrapong P - BMC Neurosci (2008)

[3H]dopamine uptake in rat brain synaptosomes. Effect of d-amphetamine and d-pseudoephedrine on [3H]dopamine uptake in rat striatal (n = 8) and nucleus accumbens (n = 4) synaptosomes. IC50 is defined as the concentration of drug producing a 50 percent inhibition in 1 nM [3H]dopamine uptake. Values represent uptake as percentage of control. IC50 values are mean ± S.E.M. from duplicate samples in each independent experiment. The IC50 values of amphetamine in inhibiting [3H]dopamine uptake in striatum and nucleus accumbens are 4.28 ± 0.47 and 2.95 ± 0.42 μM, respectively, and of d-pseudoephedrine in inhibiting [3H]dopamine uptake in striatum and nucleus accumbens are 667 ± 126 and 530 ± 61 μM, respectively.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2567327&req=5

Figure 4: [3H]dopamine uptake in rat brain synaptosomes. Effect of d-amphetamine and d-pseudoephedrine on [3H]dopamine uptake in rat striatal (n = 8) and nucleus accumbens (n = 4) synaptosomes. IC50 is defined as the concentration of drug producing a 50 percent inhibition in 1 nM [3H]dopamine uptake. Values represent uptake as percentage of control. IC50 values are mean ± S.E.M. from duplicate samples in each independent experiment. The IC50 values of amphetamine in inhibiting [3H]dopamine uptake in striatum and nucleus accumbens are 4.28 ± 0.47 and 2.95 ± 0.42 μM, respectively, and of d-pseudoephedrine in inhibiting [3H]dopamine uptake in striatum and nucleus accumbens are 667 ± 126 and 530 ± 61 μM, respectively.
Mentions: In order to investigate the mechanism of action of pseudoephedrine and to compare it to that of amphetamine, the effect of pseudoephedrine and amphetamine on [3H]dopamine uptake was assayed in synaptosomal preparations from rat brain areas. Both amphetamine and pseudoephedrine inhibited the uptake of [3H]dopamine into nucleus accumbens and striatal synaptosomes, with amphetamine being more potent than pseudoephedrine (Fig. 4). The amphetamine and pseudoephedrine curves were parallel to each other with the curve for pseudoephedrine inhibition of [3H]dopamine uptake shifted to the right. The IC50 values for amphetamine and pseudoephedrine inhibition reported here (see legend Fig. 4) indicate that amphetamine was 156 and 180 times more potent than pseudoephedrine at inhibiting [3H]dopamine uptake into striatal and nucleus accumbens synaptosomes, respectively.

Bottom Line: 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.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 pseudoephedrine.

View Article: PubMed Central - HTML - PubMed

Affiliation: Neuro-Behavioral Biology Center, Institute of Science and Technology, Research and Development, Mahidol University, Salaya, Nakornpathom, 73170, Thailand. cfncn@mahidol.ac.th

ABSTRACT

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 pseudoephedrine. 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.

Show MeSH
Related in: MedlinePlus