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Neurochemical correlates of behavioral sensitization following repeated apomorphine treatment: Assessment of the role of D 1 dopamine receptor stimulation
Author(s) -
Rowlett James K.,
Mattingly Bruce A.,
Bardo Michael T.
Publication year - 1993
Publication title -
synapse
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.809
H-Index - 106
eISSN - 1098-2396
pISSN - 0887-4476
DOI - 10.1002/syn.890140209
Subject(s) - apomorphine , neurochemical , agonist , dopamine , stimulation , chemistry , dopamine agonist , sensitization , striatum , dopamine receptor , nucleus accumbens , endocrinology , pharmacology , medicine , receptor , neuroscience , psychology , biochemistry
Abstract Previous research has revealed a role of repeated D 1 dopamine receptor stimulation in the development of behavioral sensitization to the D 1 /D 2 agonist apomorphine. The present experiments assessed the role of repeated D 1 receptor stimulation in neurochemical changes accompanying locomotor sensitization to apomorphine. To assess direct effects of D 1 stimulation on dopamine synthesis, rats were injected with the D 1 agonist SKF 38393 (8 mg/kg), followed by an injection with the 3,4‐dihydroxyphenylalanine (DOPA) decarboxylase inhibitor, NSD‐1015. DOPA accumulation, assessed in striatal, nucleus accumbens‐olfactory tubercle (NAOT), and ventral mesencephalon (VM) tissue samples, was not affected by acute SKF 38393. In the second experiment, rats were treated with 10 daily injections of vehicle, apomorphine (5 mg/kg) or the D 1 agonist SKF 38393 (8 or 16 mg/kg). Daily measures of locomotor activity demonstrated a progressive increase in the apomorphine‐treated rats, but not the SKF 38393‐treated rats, across the 10 days. On day 11, all rats were injected with NSD‐1015 for measurement of DOPA accumulation. Dopamine synthesis was enhanced in the striatum after repeated apomorphine treatment. In contrast, repeated SKF 38393 treatment resulted in either a small decrease or no change in DOPA accumulation in the different brain regions (striatum, NAOT, VM). In the third experiment, tissue levels of dopamine, 3,4‐dihydroxyphenylacetic acid (DOPAC) and [ 3 H]SCH 23390 binding to D 1 receptors were measured in rats treated with 10 daily injections of vehicle, apomorphine (5 mg/kg), or SKF 38393 (16 mg/kg). In the striatum and NAOT, none of the repeated drug treatments had an effect on DOPAC or dopamine levels. In the VM, DOPAC levels were enhanced following repeated apomorphine, but not repeated SKF 38393, whereas dopamine levels were not affected by either drug treatment. D 1 binding was not altered by the repeated drug treatments. Since repeated D 1 stimulation by SKF 38393 did not produce the same alterations in dopamine synthesis and DOPAC levels as repeated apomorphine, the neurochemical effects accompanying locomotor sensitization to apomorphine probably are not mediated by D 1 receptors. © 1993 Wiley‐Liss, Inc.