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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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Pseudoephedrine induced c-Fos expression. Western blot analysis was used to measure the acute pseudoephedrine (40 mg/kg, i.p) induced c-Fos expression in striatum and nucleus accumbens. c-Fos protein was detected 1.5 h after saline and pseudoephedrine injection.
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Figure 1: Pseudoephedrine induced c-Fos expression. Western blot analysis was used to measure the acute pseudoephedrine (40 mg/kg, i.p) induced c-Fos expression in striatum and nucleus accumbens. c-Fos protein was detected 1.5 h after saline and pseudoephedrine injection.

Mentions: The relative c-Fos response in nucleus accumbens and striatum was measured by densitometry of immunostained bands in a Western blot assay. Pseudoephedrine (40 mg/kg, i.p.) induced an acute increase in c-Fos expression in the nucleus accumbens and striatum as compared with saline-treated rats (Fig. 1). The peak c-Fos response was reached at 1.5 hours after treatment. It was maintained for up to 30 further minutes and was just above control at 3 hours after treatment (results not shown). The bands represent the 55 KDa c-Fos peptide.


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)

Pseudoephedrine induced c-Fos expression. Western blot analysis was used to measure the acute pseudoephedrine (40 mg/kg, i.p) induced c-Fos expression in striatum and nucleus accumbens. c-Fos protein was detected 1.5 h after saline and pseudoephedrine injection.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 1: Pseudoephedrine induced c-Fos expression. Western blot analysis was used to measure the acute pseudoephedrine (40 mg/kg, i.p) induced c-Fos expression in striatum and nucleus accumbens. c-Fos protein was detected 1.5 h after saline and pseudoephedrine injection.
Mentions: The relative c-Fos response in nucleus accumbens and striatum was measured by densitometry of immunostained bands in a Western blot assay. Pseudoephedrine (40 mg/kg, i.p.) induced an acute increase in c-Fos expression in the nucleus accumbens and striatum as compared with saline-treated rats (Fig. 1). The peak c-Fos response was reached at 1.5 hours after treatment. It was maintained for up to 30 further minutes and was just above control at 3 hours after treatment (results not shown). The bands represent the 55 KDa c-Fos peptide.

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