Limits...
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.

Show MeSH

Related in: MedlinePlus

Effect of chronic drug treatment on acute c-Fos response. Western blot analysis was used to measure the acute pseudoephedrine induced c-Fos expression in striatum (n = 4) and nucleus accumbens (n = 3) of rats chronically treated with pseudoephedrine (8 day treatment of pseudoephedrine twice a day with an increasing dose at 25, 30, 35, 40 mg/kg i.p., on day 1, 2, 3 and 4–8 respectively, rats were killed 1.5 h after 40 mg/kg, i.p pseudoephedrine injection on day 9). The data (quantification of bands from western blots) is expressed as percentage of c-Fos value of control animals injected with saline. (A value of 100% indicates no difference from control) Values are mean ± S.E.M. 'a' indicates significantly different from control and chronic; 'b' indicates significantly different from acute with p < 0.05.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC2567327&req=5

Figure 2: Effect of chronic drug treatment on acute c-Fos response. Western blot analysis was used to measure the acute pseudoephedrine induced c-Fos expression in striatum (n = 4) and nucleus accumbens (n = 3) of rats chronically treated with pseudoephedrine (8 day treatment of pseudoephedrine twice a day with an increasing dose at 25, 30, 35, 40 mg/kg i.p., on day 1, 2, 3 and 4–8 respectively, rats were killed 1.5 h after 40 mg/kg, i.p pseudoephedrine injection on day 9). The data (quantification of bands from western blots) is expressed as percentage of c-Fos value of control animals injected with saline. (A value of 100% indicates no difference from control) Values are mean ± S.E.M. 'a' indicates significantly different from control and chronic; 'b' indicates significantly different from acute with p < 0.05.

Mentions: To determine effect of pseudoephedrine chronic treatment, rats were chronically injected with either saline or pseudoephedrine twice a day for 8 days and sacrificed 1.5 h after a final psuedoephedrine injection on day 9. Chronic exposure to pseudoephedrine significantly reduced (p < 0.05) the acute c-Fos response to pseudoephedrine in the nucleus accumbens and striatum as compared with animals chronically treated with saline (Fig. 2).


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)

Effect of chronic drug treatment on acute c-Fos response. Western blot analysis was used to measure the acute pseudoephedrine induced c-Fos expression in striatum (n = 4) and nucleus accumbens (n = 3) of rats chronically treated with pseudoephedrine (8 day treatment of pseudoephedrine twice a day with an increasing dose at 25, 30, 35, 40 mg/kg i.p., on day 1, 2, 3 and 4–8 respectively, rats were killed 1.5 h after 40 mg/kg, i.p pseudoephedrine injection on day 9). The data (quantification of bands from western blots) is expressed as percentage of c-Fos value of control animals injected with saline. (A value of 100% indicates no difference from control) Values are mean ± S.E.M. 'a' indicates significantly different from control and chronic; 'b' indicates significantly different from acute with p < 0.05.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 2: Effect of chronic drug treatment on acute c-Fos response. Western blot analysis was used to measure the acute pseudoephedrine induced c-Fos expression in striatum (n = 4) and nucleus accumbens (n = 3) of rats chronically treated with pseudoephedrine (8 day treatment of pseudoephedrine twice a day with an increasing dose at 25, 30, 35, 40 mg/kg i.p., on day 1, 2, 3 and 4–8 respectively, rats were killed 1.5 h after 40 mg/kg, i.p pseudoephedrine injection on day 9). The data (quantification of bands from western blots) is expressed as percentage of c-Fos value of control animals injected with saline. (A value of 100% indicates no difference from control) Values are mean ± S.E.M. 'a' indicates significantly different from control and chronic; 'b' indicates significantly different from acute with p < 0.05.
Mentions: To determine effect of pseudoephedrine chronic treatment, rats were chronically injected with either saline or pseudoephedrine twice a day for 8 days and sacrificed 1.5 h after a final psuedoephedrine injection on day 9. Chronic exposure to pseudoephedrine significantly reduced (p < 0.05) the acute c-Fos response to pseudoephedrine in the nucleus accumbens and striatum as compared with animals chronically treated with saline (Fig. 2).

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