Age-related behavioural, neurochemical and radioligand binding changes in the central 5-HT system of Sprague-Dawley rats.

Abstract

Mature (3-4 months) and aged (18-19 months) Sprague-Dawley (SD) rats were treated with 5-HT receptor agonists and drug-induced behaviours monitored. The 5-HT2/1C agonist, 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI), induced wet dog shakes and back muscle contractions which were significantly increased in aged, compared to mature, rats, suggesting an age-related enhancement of 5-HT2 receptor function. In contrast, the selective 5-HT1A agonist 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT) induced forepaw treading, flat body posture, hypothermia and hyperactivity which were not significantly different in aged compared to mature rats. Levels of 5-HT and 5-hydroxyindoleacetic acid (5-HIAA) in the hippocampus and frontal cortex were measured using high performance liquid chromatography with electrochemical detection. There were no age-related changes in hippocampal 5-HT or 5-HIAA. However both 5-HT and 5-HIAA were increased in the frontal cortex of aged SD rats. 8-OH-DPAT reduced 5-HIAA in both regions examined in mature rats, an effect which was attenuated in the aged rats, suggesting an age-related reduction in presynaptic 5-HT1A receptor function. DOI did not induce any changes in 5-HT or 5-HIAA in either of the regions examined. Radioligand binding studies with [3H] ketanserin showed there to be no significant age-related changes in cortical 5-HT2 receptor density or affinity.(ABSTRACT TRUNCATED AT 250 WORDS)

• Authors: L Robson, A J Gower, D A Kendall, C A Marsden
• Journal: Psychopharmacology (Psychopharmacology (Berl)) Vol. 113 Issue 2 Pg. 274-81 ( 1993) ISSN: 0033-3158 [Print] Germany
• PMID: 7531851 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Amphetamines
• Serotonin Receptor Agonists
• Serotonin
• Hydroxyindoleacetic Acid
• 8-Hydroxy-2-(di-n-propylamino)tetralin
• Guanosine Triphosphate
• Ketanserin
• 4-iodo-2,5-dimethoxyphenylisopropylamine

Topics

• 8-Hydroxy-2-(di-n-propylamino)tetralin (pharmacology)
• Aging (metabolism, physiology)
• Amphetamines (pharmacology)
• Animals
• Behavior, Animal (drug effects)
• Binding, Competitive (drug effects)
• Brain Chemistry (physiology)
• Dose-Response Relationship, Drug
• Guanosine Triphosphate (pharmacology)
• Hydroxyindoleacetic Acid (metabolism)
• Ketanserin (pharmacokinetics)
• Male
• Radioligand Assay
• Rats
• Rats, Sprague-Dawley
• Serotonin (metabolism, physiology)
• Serotonin Receptor Agonists (pharmacology)