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Differential effects of endomorphin‐1 and ‐2 on amphetamine sensitization: Neurochemical and behavioral aspects
Author(s) -
Chen JinChung,
Liang KaiWen,
Huang Eagle YiKung
Publication year - 2001
Publication title -
synapse
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.809
H-Index - 106
eISSN - 1098-2396
pISSN - 0887-4476
DOI - 10.1002/1098-2396(20010301)39:3<239::aid-syn1005>3.0.co;2-b
Subject(s) - ventral tegmental area , amphetamine , neurochemical , dopamine , dopaminergic , striatum , chemistry , sensitization , medicine , neuroscience , endocrinology , pharmacology , psychology
Mu‐opioid receptors are known to modulate mesolimbic dopaminergic activity in the ventral tegmental area via disinhibition of GABA‐containing neurons. Recently, two novel tetrapeptides, endomorphin‐1 and endomorphin‐2, were identified in the mammalian brain and reported to have high binding affinities toward μ‐opioid receptors. To determine if endomorphins would modulate the development of amphetamine sensitization, we administered endomorphins locally into the rat brain followed by behavioral and neurochemical examinations. The results indicate that rats pretreated with endomorphin‐1 or ‐2 (5 μg per side for 7 days) in the ventral tegmental area developed locomotor sensitization to the challenge injection of amphetamine (1 mg/kg). On the other hand, when endomorphins were given in the lateral ventricle (20 μg for 5 days) of amphetamine‐sensitized rats (5 mg/kg × 14 days) during the withdrawal period (w5–w9), neither peptide had a modulatory effect on locomotor sensitization. Biochemical analyses revealed that treatment with endomorphins in the ventral tegmental area significantly increased the levels of glutamate in the medial prefrontal cortex and ventral and dorsal striatum to levels comparable to those observed in the amphetamine‐sensitized rats. In the same animals, endomorphins also caused decreases in the levels of serotonin and its metabolite, 5‐hydroxyindoleacetic acid, in the medial prefrontal cortex. Interestingly, although there was no behavioral significance, endomorphin‐1 treatment in the lateral ventricle of control and amphetamine‐sensitized rats during withdrawal resulted in decreases of GABA, aspartate, dopamine, and its metabolite 3,4‐dihydroxyphenylacetic acid in the ventral striatum. We conclude that endomorphins, by stimulating the μ‐opioid receptors in the ventral tegmental area, could sensitize the behavioral response to amphetamine. The results also demonstrate that there are differential responses between endomorphin‐1 and ‐2 on behavioral amphetamine sensitization and the underlying neurochemical substrates. Synapse 39:239–248, 2001. © 2001 Wiley‐Liss, Inc.