The effect of the dopamine agonist, apomorphine, on regional cerebral blood flow in normal volunteers

Abstract

The effect of the dopamine agonist, apomorphine, on regional cerebral blood flow in normal volunteers P. M GRASBY.T K r. FRrsroi"iJ,Liilff*.;i".PYr"tfiR FRrrH. P F LTDDLE.Fronr the MR(; Cyclotron Unit, Hatnmersmith Ho.spital; Acadentic Depurtntent of Ps1't'hiatry, Royal Frce Ho.spital and School of ltfedit'ine;National Hospitol ./br Neurolog.t'ond Neurosurger.t': Departntt,nt of' Psychologl,. UttiversitJ,College, Lorulon;and ll'{RC Clirtit'al Pharntucoktgt, Litrit, Littlentore Hospitul. Ox/ortl syNOpsrs Apomorphine, a non-selective dopamine agonist, has been used as a phannacological probe for investigating central dopaminergic neurotransmission in psychiatric illness. In this study repeated measurements of regior.ral cerebral blood Ilow (rCBF) were made in normal volunteers before. and after, the administration of apomorphine (5 or l0 7rg/kg), or placebo. The diff'erence in rCBF. before and after drug (apomorphine lcrsu.r placebo), was used to identify brain areas affected by apomorphine. Compared to placebo, both doses of apornorphine increased blood flow in the anterior cingulate cortex. Apomorphine l0 ag/kg also increased prefrontal rCBF (right > lel1). No decreases in rCBF were noted tollowing either dose of apomorphine. Apomorphine-induced increases of anterior cingulate blood flow might serve as an il lrvo inder of central dopamine function. Such an approach would complement established nenroendocrine challenge paradigms for investigating central dopamine neurotransmission in psychiatric illness. INTRODUCTIONApornorphine is a non-selective dopaurrne agonist with central and peripheral actiorrs (Anden et al. 1967', Corsini et al. l98l; Creese, 1987). It has been extensively used as a pharmacological probe of dopaminergic systems in both normal volunteers and psychiatric patients (Checkley, 1980; Meltzer et al. 1984). ln neuroendocrine challenge paradigms apomorphineinduced increases in plasma grorvth hormone are used as an index ofcentral dopamine receptor function (Checkley, 1980;Lal, 1987). Recently, an enhanced growth hormone response to apornorphine has been reported to be predictive of women at high risk of affective psychosis af ter childbirth (Wieck er ul. l99l).Despite considerable experimental data on apornorphine's central effects in animals, little rs known about the brain areas targeted, functionally, by apomorphine in humans. The use of positron emission tomography (PET) to measure drug-induced changes in regional cerebrai blood ' Address Ibr corrcspondence: Dr P. M. Grasbv. MRC Cyc)rrtron t,rnit. Hamnrersmith I'lospital, [)u Cane Road. London Wl] 0HS.

Anterior Cingulate and Subgenual Prefrontal Blood Flow Changes Following Tryptophan Depletion in Healthy Males

“…For example, the density of DA fibers in the dorsal ACC is among the highest in human cortex. Serotonergic modulation of DA has been demonstrated in vivo in humans (Smith et al, 1997), and dopaminergic manipulations are known to alter activity in human ACC (Bartlett et al, 1994;Grasby et al, 1993;Kapur et al, 1994;Paus, 2001), whereas impaired subcortical DA function is correlated with impaired performance on the Stroop Color Word interference task (Bruck et al, 2001; Rinne et al, 2000; Volkow et al, 1998), a task which activates the dorsal ACC and has altered performance following RTD.…”

Apomorphine-induced brain modulation during sexual stimulation: a new look at central phenomena related to erectile dysfunction

“…26 PET studies in normal volunteers on the effects of apomorphine alone contributed to the in vivo demonstration of the systems involved in dopamine regulation. 27,28 The rCBF increases were found in the brain regions, that receive dopaminergic projections. 29 Our data complement the results of these studies since, for the first time, they report the effects of the erotic visual stimulation in a selected series of patients during apomorphine.…”

Levodopa Challenge Neuroimaging of Levodopa-Related Mood Fluctuations in Parkinson's Disease

“…Lateral orbital cortex (BA11) is strongly implicated in regulation of mood and impulsivity, receives striatal afferents, and is influenced by dopamine, suggesting that this region may be relevant to the mood and anxiety fluctuations that differentiate our two groups of patients (Ö ngür and Price, 2000;Black et al, 2002b). A PET study of major depression identified rCBF in posterior inferior parietal lobule as correlated with anxiety (Grasby et al, 1993). In several studies, decreased metabolic activity in inferior parietal cortex (BA40) corresponds highly with state sadness or with an anxiety disorder, but the peak in Table 2 is at least 26 mm from these regions (Mayberg et al, 1999;Bremner et al, 1999a, b).…”

“…The large brainstem response to levodopa or dopamine agonists has been reported in various species, and involves a diffuse midbrain area even when assessed at much higher image resolution using [ 14 C]2-deoxyglucose and ex vivo film autoradiography (Trugman and Wooten, 1986;Grasby et al, 1993;Kapur et al, 1994;Hershey et al, 2000;Black et al, 2000). In the rodent studies, the response includes superior colliculus, midbrain reticular formation, and subthalamic nucleus.…”