Postsynaptic dopamine/adenosine interaction: I. Adenosine analogues inhibit dopamine D2-mediated behaviour in short-term reserpinized mice.
Mice pretreated with reserpine 5 mg/kg (4 h prior to the start of motor activity recording) showed locomotor activation after the administration of the D-2 agonist bromocriptine (5 mg/kg). This bromocriptine-induced locomotor activity was dose dependently inhibited by the co-administration of a D-2 antagonist (sulpiride) and dose dependently potentiated by a D-1 agonist (CY 208-243). The potentiating effect of the D-1 agonist could be inhibited by either a D-1 or a D-2 antagonist (SCH 23390 1 mg/kg or sulpiride 100 mg/kg, respectively). The bromocriptine-induced locomotor activity was not altered by either blockade of D-1 dopaminergic receptors (SCH 23390 1 mg/kg) or by co-administration of a greater dose of reserpine (10 mg/kg) plus the dopamine synthesis inhibitor, alpha-methyl-p-tyrosine (200 mg/kg). The adenosine agonists, L-PIA (a preferentially A-1 adenosine agonist) and NECA (an A-1 and A-2 adenosine agonist with above 10-fold greater affinity for A-2 than L-PIA) inhibited in a dose-dependent manner the effect of bromocriptine, NECA being above ten times more potent than L-PIA. The findings show that bromocriptine stimulates postsynaptic D-2 receptors in dopamine-depleted mice and that this effect can be inhibited by adenosine stimulation. The existence of a postsynaptic D-2/A-2 interaction is suggested, the stimulation of A-2 receptors causing an inhibition of responses elicited by postsynaptic D-2 stimulation.
Ferré
S
S
Department of Pharmacology, Karolinska Institutet, Stockholm, Sweden.
Herrera-Marschitz
M
M
Grabowska-Andén
M
M
Ungerstedt
U
U
Casas
M
M
Andén
N E
NE
D000241:Adenosine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D019830:Adenosine-5'-(N-ethylcarboxamide); D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D001971:Bromocriptine / Q000494:pharmacology; D004298:Dopamine / Q000494:pharmacology* / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D007211:Indoles / Q000494:pharmacology; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D010617:Phenanthridines / Q000494:pharmacology; D010660:Phenylisopropyladenosine / Q000494:pharmacology; D011954:Receptors, Dopamine / Q000187:drug effects*; D017448:Receptors, Dopamine D2; D012110:Reserpine / Q000494:pharmacology; D013469:Sulpiride / Q000494:pharmacology
D007211:Indoles; D010617:Phenanthridines; D011954:Receptors, Dopamine; D017448:Receptors, Dopamine D2; C054531:CY 208-243; D010660:Phenylisopropyladenosine; D019830:Adenosine-5'-(N-ethylcarboxamide); D001971:Bromocriptine; D013469:Sulpiride; D012110:Reserpine; D000241:Adenosine; D004298:Dopamine