Local administration of dopaminergic drugs into the ventral tegmental area modulates cataplexy in the narcoleptic canine.
Cataplexy in the narcoleptic canine may be modulated by systemic administration of monoaminergic compounds. In the present study, we have investigated the effects of monoaminergic drugs on cataplexy in narcoleptic canines when perfused locally via microdialysis probes in the amygdala, globus pallidus/putamen, basal forebrain, pontine reticular formation and ventral tegmental area of narcoleptic and control Doberman pinchers. Cataplexy was quantified using the Food-Elicited Cataplexy Test and analyzed by electroencephalogram, electroculogram and electromyogram. Local perfusion with the monoaminergic agonist quinpirole, 7-OH-DPAT and BHT-920, into the ventral tegmental area produced a dose-dependent increase in cataplexy without significantly reducing basal muscle tone. Perfusion with the antagonist raclopride in the same structure produced a moderate reduction in cataplexy. Local perfusion with quinpirole, 7-OH-DPAT and BHT-920 into the globus pallidus/putamen also produced an increase, while raclopride produced a decrease, in cataplexy in narcoleptic canines. In control animals, none of the above drugs produced cataplexy or muscle atonia when perfused into either the ventral tegmental area or the globus pallidus/putamen. Other monoaminergic drugs tested in these two brain areas; prazosin, yohimbine, amphetamine, SKF 38393 and SCH 23390 had no effects on cataplexy. Local perfusion with each of the above listed drugs had no effect on cataplexy in any of the other brain regions examined. These findings show that cataplexy may be regulated by D2/D3 dopaminergic receptors in the ventral tegmental area and perhaps the globus pallidus/ putamen. It is suggested that neurons in the mesolimbic dopamine system of narcoleptics are hypersensitive to dopaminergic autoreceptor agonists.
University of California at San Francisco, Langley Porter Psychiatric Institute, USA.
M S
MS
Reid
M
M
Tafti
S
S
Nishino
R
R
Sampathkumaran
J M
JM
Siegel
E
E
Mignot
D000679:Amygdala / Q000187:drug effects; D000818:Animals; D001381:Azepines / Q000494:pharmacology; D002385:Cataplexy / Q000188:drug therapy*; D004195:Disease Models, Animal; D004285:Dogs; D004298:Dopamine / Q000378:metabolism; D015259:Dopamine Agents / Q000494:pharmacology*; D018491:Dopamine Agonists / Q000494:pharmacology; D018492:Dopamine Antagonists / Q000494:pharmacology; D004569:Electroencephalography; D004576:Electromyography; D004585:Electrooculography; D005260:Female; D005917:Globus Pallidus / Q000187:drug effects; D008297:Male; D017551:Microdialysis; D011149:Pons / Q000187:drug effects; D011699:Putamen / Q000187:drug effects; D019257:Quinpirole / Q000494:pharmacology; D020891:Raclopride; D012154:Reticular Formation / Q000187:drug effects; D012457:Salicylamides / Q000494:pharmacology; D012895:Sleep, REM / Q000187:drug effects; D013764:Tetrahydronaphthalenes / Q000494:pharmacology; D017557:Ventral Tegmental Area / Q000187:drug effects* / Q000502:physiology
D001381:Azepines; D015259:Dopamine Agents; D018491:Dopamine Agonists; D018492:Dopamine Antagonists; D012457:Salicylamides; D013764:Tetrahydronaphthalenes; D019257:Quinpirole; D020891:Raclopride; C024763:talipexole; C031349:7-hydroxy-2-N,N-dipropylaminotetralin; D004298:Dopamine