Behavioural, biochemical and electrophysiological studies on the motor depressant and stimulant effects of bromocriptine.
Bromocriptine (BRC) produced a biphasic behavioural effect in mice; an early depressant phase which lasted for about 1 h and a later stimulant phase which lasted from about 1 to 5 h. The stimulation was blocked with SCH23390. Both phases of activity were accompanied by marked striatal DA autoreceptor effects as indicated by reductions in dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) levels and by a reduction in the accumulation of DOPA (after inhibition of nigrostriatal DA nerve firing and DOPA decarboxylase). However, while the autoreceptor effects were still evident during the behavioural stimulant phase, there was a gradual rise in DOPAC and HVA from 1 to 4 h after injection, indicating a gradually increasing DA turnover. We were unable, using a variety of behavioural and biochemical paradigms, to demonstrate any change in DA autoreceptor sensitivity after one dose of BRC. In electrophysiological studies, however, it was found that prior exposure of rats to one dose of BRC rendered them subsensitive to the rate-inhibiting effects of a second dose of BRC, as measured in anaesthetized animals using extracellular single cell recordings of identified DA neurons in the substantia nigra pars compacta. It is concluded firstly, that the stimulant phase of BRC in mice occurs despite continued occupation of the DA autoreceptors by BRC because adequate endogenous DA is available to provide the required D1 receptor stimulation and secondly, that the terminal autoreceptors in the striatum (as assessed in mice using biochemical techniques) may be regulated differently to the somatodendritic autoreceptors (as assessed electrophysiologically in rats).
Jackson
D M
DM
Astra Research Centre, CNS 2 Research and Development, Södertälje, Sweden.
Martin
L P
LP
Larsson
L G
LG
Cox
R F
RF
Waszczak
B L
BL
Ross
S B
SB
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000818:Animals; D001923:Brain Chemistry / Q000187:drug effects*; D001971:Bromocriptine / Q000494:pharmacology*; D004295:Dihydroxyphenylalanine / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism; D004594:Electrophysiology; D006719:Homovanillic Acid / Q000378:metabolism; D006834:Hydrazines / Q000494:pharmacology; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009043:Motor Activity / Q000187:drug effects*; D051381:Rats; D011919:Rats, Inbred Strains; D011954:Receptors, Dopamine / Q000187:drug effects / Q000378:metabolism; D013238:Stereotaxic Techniques
D006834:Hydrazines; D011954:Receptors, Dopamine; D015102:3,4-Dihydroxyphenylacetic Acid; D001971:Bromocriptine; D004295:Dihydroxyphenylalanine; C004297:3-hydroxybenzylhydrazine; D004298:Dopamine; D006719:Homovanillic Acid