Increased dopamine turnover in the ventral striatum by 8-OH-DPAT administration in the rat.
The administration of the 5-HT1A agonist 8-OH-DPAT (0.8 mumols kg-1 s.c.-40 min) produced an increase in dopamine (DA) turnover, estimated by the quotient (DOPAC + HVA) DA-1, in the ventral striatum of the rat. No statistically significant effects were obtained in the dorsal striatum. The accumulation of 3-MT in pargyline-treated animals (375 mumols kg-1 s.c.-60 min) was not affected by 8-OH-DPAT treatment (0.15-2.4 mumols kg-1 s.c.-30 min). These findings indicate that 8-OH-DPAT has weak antagonist properties at striatal DA receptors in normal rats. Both the 5-HT1A agonist flesinoxan (0.06-17.8 mumos kg-1 s.c. -50 min) and the mixed 5-HT1 and 5-HT2 agonist 5-MeODMT (1.6-26.0 mumols kg-1 s.c.-50 min) produced a decrease in forebrain 5-HTP accumulation (striatum and neocortex), following decarboxylase inhibition by means of NSD-1015 in reserpine treated rats, indicating stimulation of central 5-HT receptors by these two compounds. At the same time, the DOPA accumulation by the ventral striatum was decreased by flesinoxan and increased by 5-MeODMT treatment. These observations show that, under these conditions, the decrease in DA synthesis is not directly coupled to the decreased 5-HT synthesis produced by flesinoxan, as previously demonstrated for 8-OH-DPAT. Taken together with previous observations, the present results suggest that 8-OH-DPAT, depending on the experimental conditions, is an agonist or antagonist at striatal DA receptors, in all probability due to partial DA receptor agonist properties of the compound.
Ahlenius
S
S
Department of Neuropharmacology, Astra Research Centre, Södertälje, Sweden.
Hillegaart
V
V
Wijkström
A
A
D006916:5-Hydroxytryptophan / Q000378:metabolism; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D000818:Animals; D001711:Biotransformation; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism*; D004295:Dihydroxyphenylalanine / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism*; D008297:Male; D008732:Methoxydimethyltryptamines / Q000378:metabolism; D009281:Naphthalenes / Q000494:pharmacology*; D010879:Piperazines / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013764:Tetrahydronaphthalenes / Q000494:pharmacology*
D008732:Methoxydimethyltryptamines; D009281:Naphthalenes; D010879:Piperazines; D013764:Tetrahydronaphthalenes; C056895:flesinoxan; D004295:Dihydroxyphenylalanine; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D006916:5-Hydroxytryptophan; D004298:Dopamine