Parkinson Disease: Hockemeyer J

Salamone JD, Ishiwari K, Betz AJ, Farrar AM, Mingote SM, Font L, Hockemeyer J, Müller CE, Correa M. · Behavioral Neuroscience Division, Department of Psychology, University of Connecticut, Storrs, CT 06269-1020, USA. · Parkinsonism Relat Disord. · Pubmed #18585081 No free full text.

Abstract: Adenosine A(2A) antagonists can exert antiparkinsonian effects in animal models. Recent experiments studied the ability of MSX-3 (an adenosine A(2A) antagonist) to reverse the locomotor suppression and tremor produced by dopamine antagonists in rats. MSX-3 reversed haloperidol-induced suppression of locomotion, and reduced the tremulous jaw movements induced by haloperidol, pimozide, and reserpine. Infusions of MSX-3 into the nucleus accumbens core increased locomotion in haloperidol-treated rats, but there were no effects of infusions into the accumbens shell or ventrolateral neostriatum. In contrast, MSX-3 injected into the ventrolateral neostriatum reduced pimozide-induced tremulous jaw movements. Dopamine/adenosine interactions in different striatal subregions are involved in distinct aspects of motor function.

Salamone JD, Betz AJ, Ishiwari K, Felsted J, Madson L, Mirante B, Clark K, Font L, Korbey S, Sager TN, Hockemeyer J, Muller CE. · Department of Psychology, University of Connecticut, Storrs, CT 06269-1020, USA. · Front Biosci. · Pubmed #18508458 No free full text.

Abstract: Drug-induced tremulous jaw movements in rats have been used as a model of parkinsonian tremor. Because adenosine A2A antagonists have antiparkinsonian effects, the present experiments were conducted to study the ability of adenosine A2A antagonism to reverse the tremulous jaw movements produced by the antipsychotic drugs pimozide, haloperidol and reserpine. In one group of studies, rats received daily injections of the dopamine antagonist pimozide, and on day 8 they received injections of pimozide plus various doses of the A2A antagonists KW 6002 or MSX-3. KW 6002 and MSX-3 suppressed pimozide-induced tremulous jaw movements, reduced catalepsy, and increased locomotion. MSX-3 also suppressed the jaw movements induced by haloperidol and reserpine. In addition, local injections of MSX-3 into the ventrolateral neostriatum suppressed pimozide-induced tremulous jaw movements. Thus, adenosine A2A antagonism can reverse the tremulous movements induced by antipsychotic drugs, which is consistent with the hypothesis that antagonism of adenosine A2A receptors can result in antiparkinsonian effects. Adenosine A2A antagonists may be useful for their tremorolytic effects, and may help in treating both idiopathic and antipsychotic-induced parkinsonian symptoms.

Agnati LF, Leo G, Vergoni AV, Martínez E, Hockemeyer J, Lluis C, Franco R, Fuxe K, Ferré S. · Department of Biomedial Sciences, University of Modena and Reggio Emilia, Modena, Italy. · Brain Res Bull. · Pubmed #15342103 No free full text.

Abstract: Adenosine A2A receptors are a new target for drug development in Parkinson's disease. Some experimental and clinical data suggest that A2A receptor antagonists can provide symptomatic improvement by potentiating the effects of L-DOPA as well as a decrease in secondary effects such as L-DOPA-induced dyskinesia. L-DOPA-induced behavioral sensitization in unilateral 6-hydroxydopamine-lesioned rats is frequently used as an experimental model of L-DOPA-induced dyskinesia. In the present work this model was used to evaluate the effect of the A2A receptor agonist CGS 21680 and the A2A receptor antagonist MSX-3 on L-DOPA-induced behavioral sensitization and 6-hydroxydopamine-induced striatal dopamine denervation. L-DOPA-induced behavioral sensitization was determined as an increase in L-DOPA-induced abnormal involuntary movements and enhancement of apomorphine-induced turning behavior. Striatal dopamine innervation was determined by measuring tyrosine-hydroxylase immunoreactivity. Chronic administration of MSX-3 was not found to be effective at counteracting L-DOPA-induced behavioral sensitization. On the other hand, CGS 21680 completely avoided the development of L-DOPA-induced behavioral sensitization. The analysis of the striatal dopamine innervation showed that L-DOPA-CGS 21680 co-treatment conferred neuroprotection to the toxic effects of 6-hydroxydopamine. This neuroprotective effect was dependent on A2A and D2 receptor stimulation, since it was counteracted by MSX-3 and by the D2 receptor antagonist haloperidol. These results open new therapeutic avenues in early events in Parkinson's disease.