p Bromo methamphetamine (V III) induced improvement of learning ability in rats

J. Knoll, B. Knoll

Research output: Contribution to journalArticle

8 Citations (Scopus)


In small and medium doses amphetamine and methamphetamine enhance catecholaminergic tone; in high doses the serotonergic tone is dominant. Structure activity relationships were studied in order to synthesize more selective amphetamines. Among the new methamphetamine derivatives N1 O carboxy phenyl N2 2-2 methyl aminopropyl 1 phenylacetamidine (I 1703) is a more selective catecholaminergic amphetamine that even in high doses does not influence the serotonergic tone in the brain. Para bromo methamphetamine (V 111) is a selective serotonergic amphetamine which by long lasting inhibition of the intraneuronal 5 HT uptake first increases and afterwards decreases serotonergic tone in the brain. Daily treatment of the rats with V 111 for weeks results in a 50% decrease of the 5 HT content of the brain accompanied by an energized state of the CNS, without any sign of amphetamine like stimulation (stereotyped behavior, increased motility, resistance to tranquilizers, etc.). Even the administration of subtoxic doses of V 111 do not lead to further decrease in the 5 HT content of the brain tissue. The authors analysed the site of action of V 111 and demonstrated that the lesion of nucleus medialis raphis (MR) and of nucleus dorsalis raphis (DR) in the rat's brain results a long lasting 45.6% fall in the 5 HT content of the forebrain. The lesioned rats showed the same improvement in their learning and retention performances than rats treated chronically with V 111. Their studies with the newly synthesized amphetamines led the authors to the conclusion that the catecholaminergic and serotonergic systems antagonistically modulate the learning ability of rats. Pharmacologically induced increase of the catecholaminergic tone and more favorably a long lasting decrease in serotonergic tone improves the learning and retention performances in the rat. V 111, a new amphetamine derivative with a highly selective biochemical action on the serotonergic system of the midbrain, is a useful tool for the analysis of the role of 5 HT in the higher nervous activity of the rat.

Original languageEnglish
Pages (from-to)198-221
Number of pages24
JournalInternational Journal of Neurology
Issue number1-4
Publication statusPublished - Dec 1 1975

ASJC Scopus subject areas

  • Medicine(all)

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