Locomotor activity induced by the non-competitive N-methyl-D-aspartate antagonist, MK-801: role of nucleus accumbens efferent pathways.
We have recently shown that focal administration of dizocilpine hydrogen maleate (MK-801, a non-competitive N-methyl-D-aspartate antagonist) within the nucleus accumbens increases locomotor activity in a dopamine-independent manner. The purpose of this study was to investigate the neural network underlying locomotor stimulation induced by N-methyl-D-aspartate receptor blockade in the accumbens. In the first experiment, we examined the effect of different doses (1, 5 and 25 nmol) of the active and inactive enantiomers of the N-methyl-D-aspartate antagonist, (+)- and (-)-MK-801, respectively, focally administered in the nucleus accumbens. Only the active enantiomer induced a significant increase in locomotor activity; furthermore, the effect induced by the two highest doses of (+)-MK-801 was significantly different from that induced by (-)-MK-801. In the second part of the study, we performed ibotenic acid lesions to the major output nuclei of the accumbens, the ventral pallidum, mediodorsal thalamus, ventrolateral/ventromedial thalamus and pedunculopontine tegmental nucleus, to observe their effect on locomotor activity induced by focal (+)-MK-801 (25 nmol) administration into the accumbens. None of the lesions had any effect on spontaneous locomotor activity. Hyperactivity induced by accumbens MK-801 administrations was unaffected by ibotenic acid lesions of the pedunculopontine tegmental nucleus, while lesions of the mediodorsal thalamus induced only a partial inhibition. In contrast, ibotenic acid lesions of the ventral pallidum and ventrolateral/ventromedial thalamus completely blocked the motor response induced by accumbens MK-801. These data indicate that the intact mediodorsal thalamus, which has been proposed as a part of the loop that relays accumbens information to the prefrontal cortex, does not seem to be a structure of primary importance in MK-801 locomotor activity. On the contrary, the motor nuclei of the thalamus appear to play a more relevant role, suggesting that different neural substrates may mediate dopamine and glutamate functional output from the nucleus accumbens.
De Leonibus
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Dipartimento di Genetica e Biologia Molecolare, Università di Roma "La Sapienza", Ple. Aldo Moro 5, I-00185, Rome, Italy.
Mele
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Oliverio
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Pert
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D000818:Animals; D003714:Denervation / Q000009:adverse effects; D016291:Dizocilpine Maleate / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004525:Efferent Pathways / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D005917:Globus Pallidus / Q000187:drug effects / Q000503:physiopathology; D007051:Ibotenic Acid / Q000494:pharmacology; D008297:Male; D020645:Mediodorsal Thalamic Nucleus / Q000187:drug effects / Q000503:physiopathology; D009043:Motor Activity / Q000187:drug effects* / Q000502:physiology; D009410:Nerve Degeneration / Q000139:chemically induced; D009415:Nerve Net / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D009714:Nucleus Accumbens / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects* / Q000378:metabolism; D012154:Reticular Formation / Q000187:drug effects / Q000503:physiopathology; D020651:Ventral Thalamic Nuclei / Q000187:drug effects / Q000503:physiopathology
D018690:Excitatory Amino Acid Agonists; D018691:Excitatory Amino Acid Antagonists; D016194:Receptors, N-Methyl-D-Aspartate; D007051:Ibotenic Acid; D016291:Dizocilpine Maleate