Endogenous dopamine and dopaminergic agonists modulate synaptic excitation in neostriatum: intracellular studies from naive and catecholamine-depleted rats.
Intracellular recordings from slices of rat neostriatum were utilized to study the effects of endogenous dopamine and of exogenous dopaminergic agonists on the excitatory synaptic potentials evoked by the local stimulation of the slice. D-Amphetamine (0.1-5 microM), as well as dopamine, produced a dose-dependent decrease of the excitatory synaptic potentials. This effect was blocked by membrane hyperpolarization. The blockade of potassium channels by intracellular cesium or by extracellular 4-aminopyridine (0.5-1 mM) did not block the voltage-dependent effect of dopamine. The effects of D-amphetamine were antagonized by (R)-(+)-8-chloro-2,3,4,5-tetrahydro-3-methyl-5-phenyl-1H-3-benzazepine-7 -ol (SCH 23390) (0.1-1 microM), an antagonist for D1 dopaminergic receptors, but not by sulpiride (0.1-1 microM), an antagonist for D2 receptors. Pretreatment of the animals with alpha-methyl-p-tyrosine (200 mg/kg) or with reserpine (5 mg/kg) blocked the amphetamine-induced effect on the synaptic potentials. In reserpinized animals, the hyperpolarization of the membrane potential did not block the dopamine-induced decrease of the synaptic excitation. After reserpine pretreatment bromocryptine and lysuride, D2 agonists which in control conditions were ineffective, also mimicked the effects of dopamine. In reserpinized rats, the inhibitory effects of the dopaminergic agonists were antagonized by sulpiride, but not by SCH 23390. We conclude that in naive animals endogenous dopamine mimics the voltage-dependent reduction of synaptic excitation produced by D1 activation, while in catecholamine-depleted rats dopamine lacks its voltage-dependent effect and interacts with "supersensitive" D2 receptors.
Calabresi
P
P
Dipartimento di Sanita Pubblica, II Universita degli Studi di Roma, Italy.
Benedetti
M
M
Mercuri
N B
NB
Bernardi
G
G
D015761:4-Aminopyridine; D000200:Action Potentials / Q000187:drug effects; D000631:Aminopyridines / Q000494:pharmacology; D000662:Amphetamines / Q000494:pharmacology; D000818:Animals; D001552:Benzazepines / Q000494:pharmacology*; D001971:Bromocriptine / Q000494:pharmacology; D002395:Catecholamines / Q000378:metabolism / Q000502:physiology*; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D004298:Dopamine / Q000378:metabolism / Q000502:physiology*; D015259:Dopamine Agents / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D015221:Potassium Channels / Q000187:drug effects / Q000502:physiology; D051381:Rats; D011919:Rats, Inbred Strains; D013469:Sulpiride / Q000494:pharmacology
D000631:Aminopyridines; D000662:Amphetamines; D001552:Benzazepines; D002395:Catecholamines; D015259:Dopamine Agents; D015221:Potassium Channels; D001971:Bromocriptine; D013469:Sulpiride; D015761:4-Aminopyridine; D004298:Dopamine