Behavioural effects of selective serotonin reuptake inhibitors following direct micro injection into the left red nucleus of the rat.
The behavioural effects of selective serotonin reuptake inhibitors (paroxetine, sertraline, citalopram, fluvoxamine, fluoxetine) and reference compounds (N,N'-di(o-tolyl)guanidine, haloperidol, 3-(3-hydroxyphenyl)-N-(l-propyl)piperidine and chlorpromazine) were studied for their ability to produce dystonia and torticollis following direct micro injection into the left red nucleus of the rat, an area of the brain containing a high density of sigma2 receptors but relatively devoid of biogenic amine receptors. Each animal was monitored for abnormalities in posture and movement for a period of 30 min and then sacrificed 40 min following drug administation. Only fluvoxamine (100 nmol) and fluoxetine (100 nmol) elicited acute dystonic behaviour (1-5 min). The onset of dystonia was accompanied by facial spasticity, vacuous chewing movements and grooming behaviour which reflected the extent of dystonia. The dystonic behaviour following the direct intrarubal injection of fluvoxamine and fluoxetine suggest the possible activation of sigma2 receptors while citalopram, sertraline and paroxetine were without effect. The results of this study support the role of sigma2 receptors in the regulation and control of movement and coordination and provides preliminary evidence to suggest the in vivo activity of sigma receptors by fluoxetine and fluvoxamine.
Faherty
C J
CJ
Department of Pharmacology, University College, Galway, Ireland.
Earley
B
B
Leonard
B E
BE
D015057:1-Naphthylamine / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects* / Q000502:physiology; D002746:Chlorpromazine / Q000494:pharmacology; D015283:Citalopram / Q000494:pharmacology; D005473:Fluoxetine / Q000494:pharmacology; D016666:Fluvoxamine / Q000494:pharmacology; D006146:Guanidines / Q000494:pharmacology; D006220:Haloperidol / Q000494:pharmacology; D008297:Male; D008845:Microinjections; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D017374:Paroxetine / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D011187:Posture / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017480:Receptors, sigma / Q000187:drug effects / Q000502:physiology; D012012:Red Nucleus / Q000187:drug effects* / Q000502:physiology; D017367:Selective Serotonin Reuptake Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D020280:Sertraline
D015057:1-Naphthylamine; D002746:Chlorpromazine; D015283:Citalopram; D005473:Fluoxetine; D016666:Fluvoxamine; D006146:Guanidines; D006220:Haloperidol; D017374:Paroxetine; D010880:Piperidines; D017480:Receptors, sigma; D017367:Selective Serotonin Reuptake Inhibitors; D020280:Sertraline; C026539:preclamol; C050232:1,3-ditolylguanidine