Effects of the local application of 3-PPP and sulpiride enantiomers into the nucleus accumbens or into the ventral tegmental area on rat locomotor activity: evidence for the functional importance of somatodendritic autoreceptors.
The present series of experiments was performed in order to determine the relative role of presynaptic and somato-dendritic autoreceptors for the sedative effects produced by systemically administered dopaminergic agonists. Thus, the effects of intracerebral administration of 3-(3-hydroxyphenyl)-N-n-propylpiperidine (3-PPP), or sulpiride, enantiomers on spontaneous locomotor activity was investigated in rats. It was found that the local application of (-)3-PPP, but not (+)3-PPP, into the nucleus accumbens (1.25-80.0 micrograms, bilaterally) produced a suppression of the locomotor activity, whereas the local application of the two enantiomers into the ventral tegmental area resulted in a suppression of the locomotor activity in the same dose range. Thus, the full dopamine D2 agonist (+)3-PPP produced suppression of locomotor activity only after local application into the somato-dendritic region, suggesting that in terminal areas postsynaptic receptor stimulation effectively counterbalanced the functional consequences of presynaptic receptor stimulation. The sulpiride enantiomers both produced a suppression of locomotor activity after local application into the accumbens (0.2-5.0 micrograms, bilaterally). In the ventral tegmental area, however, (-)sulpiride administration (0.2-5.0 micrograms, bilaterally) resulted in an increased locomotion, whereas the (+)enantiomer produced no effect or, at the highest dose (5.0 micrograms), a suppression of the locomotor activity. These observations indicate that for a dopamine D2 antagonist, the postsynaptic receptor blockade in the terminal region, resulting in behavioral suppression, not only counteract compensatory effects produced via the presynaptic receptor in this region, but also to a great extent overshadow the functional consequences of somatodendritic autoreceptor blockade.(ABSTRACT TRUNCATED AT 250 WORDS)
Department of Neuropharmacology, Astra Research Centre, Södertälje, Sweden.
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D000818:Animals; D015259:Dopamine Agents / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D009043:Motor Activity / Q000187:drug effects*; D009714:Nucleus Accumbens / Q000187:drug effects*; D010880:Piperidines / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D011954:Receptors, Dopamine / Q000502:physiology*; D013469:Sulpiride / Q000008:administration & dosage / Q000494:pharmacology*; D013681:Tegmentum Mesencephali / Q000187:drug effects*
D015259:Dopamine Agents; D010880:Piperidines; D011954:Receptors, Dopamine; D013469:Sulpiride; C026539:preclamol