Progressive pathology of the caudate nucleus, the substantia nigra pars reticulata and the deeper layers of the colliculus superior: acute behavioural and metabolic effects of intrastriatal kainic acid.
The acute behavioural and metabolic consequences of functional changes following unilateral intracaudate kainic acid at the level of the feline caudate nucleus, the substantia nigra pars reticulata and the deeper layers of the colliculus superior were investigated. The present study became possible since it was previously found that unilateral changes in neurotransmission processes in these structures all result in behavioural alterations that can be distinguished from each other. During the first 17 min after kainic acid, all animals displayed contralateral forced staccato head turning; these movements are characteristic for an activation of dopamine receptors and/or inhibition of GABA receptors in the rostromedial caudate nucleus. Between 15 and 50 min, all animals displayed fast, uninterrupted contralateral forced head, torso or body turning; these movements are characteristic for an activation of nigral GABA receptors. From about 48 min, all animals displayed sequences of short contralateral forced ear, head, torso and body turnings; these movements are characteristic for an inhibition of collicular GABA receptors. Furthermore, most cats displayed ipsilateral orofacial dyskinetic movements during the whole 180 min observation period. Metabolism was analysed in three cats that received [14C]2-D-deoxyglucose immediately before, 5 min after, or 70 min after kainic acid. Metabolism was increased in the ipsilateral caudate nucleus; this effect was most pronounced in the cat that received deoxyglucose immediately before kainic acid. Metabolic activity was increased in the ipsilateral substantia nigra pars reticulata; this effect was most pronounced in the cat treated with deoxyglucose 5 min after kainic acid. Metabolism was increased in the ipsilateral deeper layers of the colliculus superior in the cat that received deoxyglucose 70 min after kainic acid. The present behavioural and metabolic data suggest that kainic acid produces an increasing pathology resulting successively in functional changes in the caudate nucleus, its output-station the substantia nigra pars reticulata and the nigral output-station the deeper layers of the colliculus superior. It is suggested that the successive appearance of the latter effects is inherent in the hierarchical order of the brain structures under study. The occurrence of orofacial dyskinetic movements during the whole observation period suggests that the former movements were not mediated via the striato-nigro-collicular pathway. Finally, apomorphine injected in the ipsilateral caudate nucleus 1 week after kainic acid was significantly less effective compared to apomorphine injected 1 week before kainic acid. The c
Psychoneuropharmacological Research Unit, University of Nijmegen, The Netherlands.
R M
RM
Jaspers
J W
JW
Berkelbach van der Sprenkel
A R
AR
Cools
D000818:Animals; D001058:Apomorphine / Q000494:pharmacology; D001522:Behavior, Animal / Q000187:drug effects*; D002415:Cats; D002421:Caudate Nucleus / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D003847:Deoxyglucose / Q000378:metabolism; D007608:Kainic Acid / Q000494:pharmacology*; D008297:Male; D013378:Substantia Nigra / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology / Q000502:physiology*; D013477:Superior Colliculi / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology
D003847:Deoxyglucose; D001058:Apomorphine; D007608:Kainic Acid