ABSTRACT
The effects of daily bilateral microinjections of GABA-A receptor antagonist picrotoxin (2 mcg) into rostral neostriatum of the rats in chronic experiments were investigated. The picrotoxin was injected in volume of 1 mcl of saline or in 1 mcl of 1.0 M or 1.5 M MgCl2 solution; 1 mcl of saline or 1.0 M MgCl2 solution were injected in control groups of animals. The impairment of the avoidance conditioning in shuttle box, changes in free locomotor activity and the stereotypic choreo-myoclonic limb jerks were registered in rats with picrotoxin with the saline microinjections. The motor deviation registered are similar with Huntington chorea hyperkinesis in humans. The addition of magnesium ions into injected solution prevented both the lyperkinesis and condition behaviour realization impairment. As the magnesium is a universal calcium channel blocker, the calcium homeostasis of striatal neurons impairment as one of principal elements of hyperkinesis pathogenesis is proposed.
Subject(s)
Calcium Signaling/drug effects , Hyperkinesis/prevention & control , Magnesium/administration & dosage , Neostriatum/drug effects , Animals , Calcium Channels/drug effects , Cations, Divalent/administration & dosage , GABA Antagonists/toxicity , Hyperkinesis/chemically induced , Male , Microinjections , Neostriatum/physiopathology , Picrotoxin/toxicity , Rats , Rats, WistarABSTRACT
It was shown in chronic rat experiments that multiple microinjections of furosemide into the rostral region of the neostriatum facilitated avoidance conditioning in a shuttle box and prevented from GABA-induced deviant freezing, but did not abolish the choreic hyperkinesis produced by picrotoxine (GABA-A receptors antagonist) intrastriatal microinjections. Simultaneous microinjections of furosemide and picrotoxine into the neostriatum increased differences in parameters of picrotoxine-induced hyperkinesis between rat groups capable and incapable (extinct reflex) for conditioned avoidance. These findings point to a certain correlation between the intensity of hyperkinesis, capability for acquisition and realization of avoidance conditioning, and activity of neostriatal neurotransmitter systems involved in neuronal homeostasis. The findings suggest an involvement of neostriatal GABAergic system in conditioning and organization of free locomotor behavioral acts.
Subject(s)
Behavior, Animal/drug effects , Furosemide/pharmacology , Neostriatum/physiology , Picrotoxin/pharmacology , Sodium Potassium Chloride Symporter Inhibitors/pharmacology , gamma-Aminobutyric Acid/pharmacology , Animals , Avoidance Learning/drug effects , Conditioning, Classical/drug effects , GABA-A Receptor Antagonists , Male , Microinjections , Neostriatum/drug effects , Rats , Rats, WistarABSTRACT
The effects of daily intrastriatal bilateral microinjections of 45 mog GABA, 1 mcg of picrotoxine and 5 mcg of bicuculline on rats, were investigated. Impairment of the avoidance conditioning in shuttle box was registered in rats with picrotoxine or bicuculline and the choreo-myoklonic limb jerks, with distinct generalization stage after the picrotoxine microinjections. The combined microinjections--GABA with picrotoxine, and bicuculline with picrotoxine inhibited the hyperkinesis manifestation and changed avoidance conditioning behaviour and open-field locomotor activity. The findings suggest involvement of neostriatal GABAergic system in avoidance conditioning and complex locomotor behavioural acts regulation. The ultimate aim of the research is to find the cause, neurotransmitter mechanisms of neuromotor diseases, and to research principal new orders in treatment of neuromotor deviations.
