Behavioral and neurochemical effects of dopaminergic drugs in models of brain injury.
The dopaminergic drugs, ropinirole and dihydroergocryptine (DHECP) were injected subcutaneously (s.c.) at doses of 0.5 and 1 mg/kg/day for 7 days into male rats of the Sprague-Dawley strain. The drug pretreatment reverted amnesia induced in rats by hypobaric hypopxia and tested in active and passive avoidance tasks. Furthermore, a partial restoration of memory retention was found in animals with a 2-month brain occlusive ischemia induced by manipulation of the four major arteries of the brain. No major changes were found in spontaneous motor activity, but drug treatment increased ambulation of animals subjected to acute or chronic experimental manipulation. In a model of kainate-induced epilepsy, ropinirole or DHECP did not affect seizure parameters, but reduced mortality rate. At the end of behavioral procedures, in all animals subjected to hypobaric hypoxia or to brain occlusive ischemia glutathione redox index (glutathione reduced/glutathione oxidized ratio) was measured in the frontal cortex, striatum and hippocampus. It was found that experimental models of brain injury were followed by a decrease of reduced glutathione content in all brain areas. The glutathione redox index was augmented by ropinirole or DHECP treatment in all brain areas. These behavioral and neurochemical findings suggest that ropinirole and DHECP may exert either protective activity (as found in animals pretreated with these drugs and exposed to hypobaric hypoxia) or reversal of brain injury (as found in animals treated after two-month occlusive brain ischemia). Thus, both drugs may be studied as therapeutic agents in brain injuries of various origin.
Medico
M
M
Department of Experimental and Clinical Pharmacology, University of Catania, Catania, Italy.
De Vivo
S
S
Tomasello
C
C
Grech
M
M
Nicosia
A
A
Castorina
M
M
D'Agata
M A
MA
Rampello
L
L
Lempereur
L
L
Drago
F
F
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects* / Q000502:physiology; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D001930:Brain Injuries / Q000188:drug therapy* / Q000378:metabolism; D025443:Dihydroergocryptine / Q000494:pharmacology / Q000627:therapeutic use; D004195:Disease Models, Animal; D015259:Dopamine Agents / Q000494:pharmacology / Q000627:therapeutic use; D018491:Dopamine Agonists / Q000494:pharmacology* / Q000627:therapeutic use*; D005978:Glutathione / Q000378:metabolism; D007211:Indoles / Q000494:pharmacology / Q000627:therapeutic use; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley
D015259:Dopamine Agents; D018491:Dopamine Agonists; D007211:Indoles; C046649:ropinirole; D025443:Dihydroergocryptine; D005978:Glutathione