ABSTRACT
This study examined the [3H]5-HT-releasing properties of 3,4-methylenedioxymethamphetamine (MDMA) and related agents, all of which cause significant release of [3H]5-HT from rat brain synaptosomes. 5-HT uptake blockers dose dependently block MDMA-induced [3H]5-HT release. The EC50s of the uptake drugs in blocking MDMA-induced release correlate with their affinity for the 5-HT uptake site labeled by [3H]paroxetine (r = 0.98; P less than 0.01). These data demonstrate that the 5-HT uptake carrier plays a significant role in the release of 5-HT induced by MDMA and related agents.
Subject(s)
3,4-Methylenedioxyamphetamine/antagonists & inhibitors , Amphetamines/antagonists & inhibitors , Serotonin Antagonists/pharmacology , Serotonin/metabolism , 3,4-Methylenedioxyamphetamine/analogs & derivatives , 3,4-Methylenedioxyamphetamine/pharmacology , Animals , Brain Chemistry/drug effects , In Vitro Techniques , Male , N-Methyl-3,4-methylenedioxyamphetamine , Paroxetine , Piperidines/pharmacology , Rats , Rats, Inbred Strains , Synaptosomes/drug effects , Synaptosomes/metabolismABSTRACT
3,4-Methylenedioxymethamphetamine (MDMA; 'Ecstasy') is a known neurotoxin to 5-hydroxytryptamine (5-HT) nerve terminals. Recent studies have suggested that endogenous dopamine (DA) and/or 5-HT may mediate the MDMA-induced neurotoxicity. The central monoamine stores of rats were significantly decreased with reserpine (5 mg/kg) prior to toxic injections of MDMA. Rats given MDMA (30 mg/kg) displayed significant decreases in the density of 5-HT nerve terminals labeled by [3H]paroxetine both with (51 +/- 8%) and without (43 +/- 20%) reserpine pre-treatment. These data suggest that the degeneration of 5-HT nerve terminals following MDMA is independent of the presence of endogenous stores of DA or 5-HT.
Subject(s)
3,4-Methylenedioxyamphetamine/toxicity , Amphetamines/toxicity , Designer Drugs/toxicity , Nervous System Diseases/chemically induced , Reserpine/therapeutic use , 3,4-Methylenedioxyamphetamine/analogs & derivatives , Animals , Cerebral Cortex/drug effects , Cerebral Cortex/metabolism , Corpus Striatum/drug effects , Corpus Striatum/metabolism , Dopamine/metabolism , Male , N-Methyl-3,4-methylenedioxyamphetamine , Nerve Endings/metabolism , Nervous System Diseases/metabolism , Nervous System Diseases/prevention & control , Paroxetine , Piperidines/metabolism , Rats , Rats, Inbred Strains , Reserpine/pharmacology , Serotonin/metabolismABSTRACT
The past decade has seen important advances in the clinical utility of serotonergic agents. The putative novel anxiolytic effects of 5-HT1A partial agonists such as buspirone, the antidepressant effects of selective serotonin (5-HT) uptake blockers such as fluoxetine, and the unique and potent antiemetic effects of 5-HT3 antagonists in cancer chemotherapy are excellent examples of the clinical relevance of selective 5-HT receptor agents. The increasing ability to modulate serotonergic neurotransmission through distinct 5-HT receptor subtypes should greatly facilitate the analysis of 5-HT in both normal and abnormal human brain function.
Subject(s)
Neurocognitive Disorders/drug therapy , Psychotropic Drugs/therapeutic use , Receptors, Serotonin/drug effects , Serotonin Antagonists/therapeutic use , Serotonin/physiology , Synaptic Transmission/drug effects , Animals , Anxiety Disorders/drug therapy , Anxiety Disorders/physiopathology , Brain/drug effects , Brain/physiopathology , Depressive Disorder/drug therapy , Depressive Disorder/physiopathology , Humans , Neurocognitive Disorders/physiopathology , Receptors, Serotonin/classification , Receptors, Serotonin/physiology , Synaptic Transmission/physiologyABSTRACT
Cerebral contusion was caused in 18 rats by dropping various weights on an exposed dura of one hemisphere. One or 3 hours after the injury the animals were sacrificed by perfusion with paraformaldehyde-glutaraldehyde solution. The traumatic microvascular and neural tissue alterations were studied with light, scanning, and electron microscopic techniques. The microvascular obstructions and damage were revealed in this study as major histological alterations, causing secondary neural damage. The obstruction of the vessels appeared to have been caused 1) by extravascular pressure from destroyed and swollen tissue, petechial hemorrhage, and dissecting extraluminal clots; and 2) by intravascular clots. Besides the tearing and shearing effects causing petechial hemorrhages, the capillary walls were often thinned and irregular.