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- W2078383982 abstract "This study was designed to evaluate the effects of a chronic treatment with the classical neuroleptic drug haloperidol on the preproenkephalin (ppEnk) mRNA synthesis and its consequences for opioid and dopamine (DA) receptor-regulated adenylate cyclase in the developing and adult rat striatum. In situ hybridization experiments revealed that the tonic inhibitory effect of DA on striatal ppEnk mRNA synthesis gradually develops postnatally and seems to be dependent on the presence of adenylate cyclase-coupled D2 receptors. In addition, postnatal treatment with haloperidol resulted in a clear reduction of D1 DA receptor-stimulated cAMP production and a profound desensitization of δ-opioid receptors inhibitory coupled to adenylate cyclase. These adaptive changes may underlie the well-known increase in locomotor and reinforcing effects of μ opioids upon chronic neuroleptic treatment. The basal ganglia contain high levels of dopamine (DA) and enkephalins and numerous functional relationships between both neurotransmitter systems have been reported. DA seems to exert a tonic inhibition on the availability of endogenous enkephalins in the nucleus accumbens and striatum, since chronic treatment with DA antagonists or destruction of dopaminergic neurons by 6-OHDA has been shown to cause an increased expression, content and release of these neuropeptides (1,2,3). A major role of the D2 receptor in the regulation of the enkephalin mRNA expression and peptide levels has been consistently reported. Enkephalin-containing neurons in the striatum can be detected as early as embryonic day 16 (E16) in rat brain (4). Interestingly, we found recently that DA receptors in the rat striatum develop rather asynchroniously. Whereas the stimulatory coupling of D1 receptors to adenylate cyclase occurs in the prenatal period (E17), D2 receptor-mediated inhibition of cAMP production can not be detected until the second postnatal week (5). Since the cAMP pathway seems to play an important role in the regulation of the expression of the preproenkephalin gene (6,7,8), we decided to study the ontogeny of the dopaminergic control of enkephalin synthesis. In addition, we determined the consequences of an enhanced enkephalin availability in the striatum, induced by chronic haloperidol treatment, for the effect of Met-enkephalin on DA-regulated adenylate cyclase activity during different developmental stages." @default.
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- W2078383982 date "1994-02-01" @default.
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- W2078383982 title "Changes in rat striatal ppENK expression and adenylate cyclase-coupled opioid receptors upon haloperidol treatment during different developmental stages" @default.
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- W2078383982 doi "https://doi.org/10.1016/0167-0115(94)90284-4" @default.
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