E-Locus - Institutional Repository of the University of Crete - Νευροπροστατευτικές επιδράσεις του συνθετικού κανναβινοειδούς HU-210 έναντι της προκαλούμενης από την 5,7-DHT σερετονινεργικής τοξικότητας in vivo. Προεκτάσεις στη νεθροτοξικότητα της MDMA και των αντίστοιχων αμφεταμινικών παραγώγων

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Identifier

000374871

Title

Νευροπροστατευτικές επιδράσεις του συνθετικού κανναβινοειδούς HU-210 έναντι της προκαλούμενης από την 5,7-DHT σερετονινεργικής τοξικότητας in vivo. Προεκτάσεις στη νεθροτοξικότητα της MDMA και των αντίστοιχων αμφεταμινικών παραγώγων

Alternative Title

Neuroprotective effects of the syntetic cannabinoid HU-210against 5,7-dihydroxytryptamine serotonergic toxicity in vivo extensions in MDMA and other related substituted amphetamines neurotoxicity

Author

Φώκος, Στέφανος

Thesis advisor

Θερμού, Κική

Reviewer

Καστελλάκης, Ανδρέας
Παναγής, Γιώργος

Abstract

Several cannabinoids have been shown capable of providing neuroprotection against different neurotoxic procedures and therefore seem to be effective in the treatment of several neurodegenerative disorders. Furthermore, some substituted amphetamines (METH, MDMA) are strong serotonergic and dopaminergic neurotoxins. Similar pathogenic procedures are implicated in the manifestation of most neurodegenerative disorders and in the substituted amphetamines induced neurotoxicity. In this study, we examined the effects of chronic i.p. administration of HU-210, a potent cannabinoid agonist, after i.c.v. injection of 5,7-DHT, a strong serotonergic neurotoxin. The serotonergic lesion was estimated by calculation of the 5-HT and 5-HIAA levels using HPLC technique as well as by calculation of SERT density using [3H]paroxetine binding. Our results showed that 5,7-DHT injection significantly reduced 5-HT content in hippocampus and striatum, 5-HIAA content and [3Η]paroxetine binding in hippocampus and induced significant increase in 5-HT turnover (5-HIAA/5-HT) in both cerebral regions mentioned above. Moreover, the chronic HU-210 treatment reversed all 5,7-DHT neurotoxic effects, restoring, in some cases, the levels of serotonergic indexes. HU-210 treatment without the presence of the toxin did not alter the levels of estimated indexes showing that HU-210 induced serotonergic effect was the result of a neuroprotection procedure than a chronic administration upregulatory effect. Our findings show for the first time that cannabinoids are capable of providing neuroprotection against 5,7-DHT induced serotonergic degeneration and, therefore, may be used in the future in the treatment of similar neurotoxic conditions in humans. Substituted amphetamines are extensively used among humans for recreational purposes often in combination of cannabis use. Our findings may, at least partially, explain in these cases the lack of serotonergic toxicity evidence in humans.

Language

Greek

Subject

5,7-dihydroxitryptamine

5,7-Διυδροξυτρυπταμίνη

Cannabinoids

Neuroprotection

Neurotoxicity

Pharmacology

SERT

Serotonin

Substituted amphetamines