Compelling evidence indicates that oxidative stress contributes to motor neuron injury in amyotrophic lateral sclerosis (ALS), but antioxidant therapies have not yet achieved therapeutic benefit in the clinic. The nuclear erythroid 2-related-factor 2 (Nrf2) transcription factor is a key regulator of an important neuroprotective response by driving the expression of multiple cytoprotective genes...

Objective(s) While the nucleus accumbens and the striatum have received much attention regarding their roles in stereotyped behaviors, the role of the medial prefrontal cortex (mPFC) has not been investigated to the same degree. Few studies have reported the role of the mPFC in dopaminergic induction of locomotor hyperactivity. The mPFC is a heterogeneous area (the anterior cingulated, prelimbi...

On most adrenergic and cholinergic nerve terminals, prejunctional α-adrenoceptors belonging to the α2-subtype have been identified. Activation of these receptors will decrease the release of norepinephrine. It has been reported that several isolated tissue preparations contain prejunctional dopamine receptors, the stimulation of which inhibits neurotransmission. It has remained uncertain whethe...

Following unilateral striatal dopamine depletion, the hemiparkinsonian rat exhibits rotational behavior in response to amphetamine and apomorphine. The rotational behaviors induced by these drugs are thought to reflect an asymmetry in presynaptic striatal dopamine release and an asymmetry in postsynaptic striatal dopamine receptor function, respectively. Grafts of adrenal medulla cells in the l...

Although certain antiparkinson agents interact with serotonin (5-HT) receptors, little information is available concerning functional actions. Herein, we characterized efficacies of apomorphine, bromocriptine, cabergoline, lisuride, piribedil, pergolide, roxindole, and terguride at human (h)5-HT(1A), h5-HT(1B), and h5-HT(1D) receptors [guanosine 5'-O-(3-[(35)S]thio)triphosphate ([(35)S]GTPgamma...

The authors examined the effect of local administration of a dopamine receptor agonist on visual deprivation-induced excessive ocular growth and myopia. Eight rhesus monkeys were monocularly deprived of vision from birth with opaque contact lenses. Four of the monkeys received drops of 1% apomorphine HCl 2-3 times/day in the occluded eye; the four control monkeys received vehicle only. Axial le...

Several lines of evidence suggest a role for dopamine in the control of suicidal behaviour. Previously, we suggested an involvement of D2-dopaminergic function in the biology of suicide by demonstrating a smaller growth hormone (GH) response to apomorphine, a dopaminergic agonist, in depressed patients who later died by suicide. The purpose of the present study was to assess GH response to apom...

Five patients with idiopathic Parkinson's disease with severe response fluctuations were selected for a randomized double-blind placebo-controlled study, concerning the clinical effects of subcutaneous apomorphine and its assessment in 'off'-periods. The study was designed as five n = 1 studies, in which every patient was his own control. The effect of apomorphine was studied by using the Colum...

The antiemetic properties of a novel neurokinin-1 (NK1) receptor antagonist, FK886 ([3,5-bis(trifluoromethyl)phenyl][(2R)-2-(3-hydroxy-4-methylbenzyl)-4-{2-[(2S)-2-(methoxymethyl)morpholin-4-yl]ethyl}piperazin-1-yl]methanone dihydrochloride), were studied in dog models of cisplatin- and apomorphine-induced emesis. Intravenously administered FK886 (0.32-1 mg/kg) significantly inhibited cisplatin...