Effects of B-HT 920 on nigrostriatal and mesolimbic dopamine systems in normosensitive and supersensitive rats.
1. B-HT 920, a D2 dopamine receptor agonist, was tested for its ability to exert presynaptic actions in normosensitive rats, and for possible postsynaptic actions in rats made 'supersensitive' to apomorphine. 2. In normosensitive rats, B-HT 920 (0.01-0.3 mg kg-1, i.p.) increased dopamine concentrations and lowered metabolite levels to a similar extent in all four terminal regions examined (medial prefrontal cortex, olfactory tubercle, nucleus accumbens, caudate-putamen). Analogous effects were seen for 5-hydroxytryptamine and its metabolite 5-hydroxyindoleacetic acid. 3. Rats which received bilateral 6-hydroxydopamine (6-OHDA) infusions into the caudate-putamen showed signs of postsynaptic dopamine receptor activation (stereotyped behaviour) in response to B-HT 920 (0.1 and 1.0 mg kg-1, i.p.) and to apomorphine (0.2 mg kg-1, s.c.). Similarly, B-HT 920 (0.1 mg kg-1) induced contralateral circling in rats that had received unilateral 6-OHDA infusions into the medial forebrain bundle; the rate of circling increased gradually over several weeks. 4. In contrast, bilateral 6-OHDA infusions into the nucleus accumbens resulted in a supersensitive (locomotor stimulant) response to a low dose of apomorphine (0.1 mg kg-1, s.c.), but not to B-HT 920 (0.01 and 0.1 mg kg-1). 5. In intact rats, withdrawal of chronic haloperidol treatment induced behavioural supersensitivity to apomorphine but not to B-HT 920.
Clarke
P B
PB
Department of Psychiatry, University of British Columbia, Vancouver, Canada.
Wyder
K J
KJ
Jakubovic
A
A
Fibiger
H C
HC
D000818:Animals; D001058:Apomorphine / Q000494:pharmacology; D001381:Azepines / Q000494:pharmacology*; D015306:Biogenic Monoamines / Q000378:metabolism; D001923:Brain Chemistry / Q000187:drug effects; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism*; D004298:Dopamine / Q000502:physiology*; D006220:Haloperidol / Q000494:pharmacology; D006892:Hydroxydopamines / Q000494:pharmacology; D008032:Limbic System / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008474:Medial Forebrain Bundle / Q000187:drug effects / Q000378:metabolism; D009043:Motor Activity / Q000187:drug effects; D009714:Nucleus Accumbens / Q000187:drug effects / Q000378:metabolism; D016627:Oxidopamine; D010293:Pargyline / Q000494:pharmacology; D051381:Rats; D013239:Stereotyped Behavior / Q000187:drug effects; D013378:Substantia Nigra / Q000187:drug effects / Q000378:metabolism*
D001381:Azepines; D015306:Biogenic Monoamines; D006892:Hydroxydopamines; C024763:talipexole; D016627:Oxidopamine; D010293:Pargyline; D006220:Haloperidol; D001058:Apomorphine; D004298:Dopamine