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Use of antisense oligodeoxynucleotide to determine delta-opioid receptor involvement in [D-Ala2]deltorphin II-induced
H Mizoguchi1, M Narita, H Nagase
1Department of Anesthesiology, Medical College of Wisconsin, Milwaukee 53226, USA.
Abstract:
Intracerebroventricularly (i.c.v.)-administered [D-Ala2]deltorphin II (20 micrograms) produced a marked locomotor hyperactivity in male ICR mice. The locomotor hyperactivity induced in response to i.c.v. [D-Ala2]deltorphin II (20 micrograms) was suppressed by pretreatment with naltriben (NTB, 10 micrograms) but not 7-benzylidene naltrexone (BNTX, 1 microgram) and D-Phe-Cys-Tyr-D-Try-Orn-Thr-Phe-Thr-NH2 (CTOP, 100 ng). The influence of antisense oligodeoxynucleotide to delta-opioid receptor mRNA (delta-AS oligo) or a mismatch oligodeoxynucleotide (MM oligo) on the locomotor hyperactivity induced by [D-Ala2]deltorphin II was determined. Groups of mice pretreated i.c.v. with delta-AS oligo (1 microgram), MM oligo (1 microgram) or saline (4 microliters) once a day for 3 days, were injected i.c.v. [D-Ala2]deltorphin II (10 or 20 micrograms) and the locomotor response to [D-Ala2]deltorphin II was measured. The locomotor hyperactivity of i.c.v. [D-Ala2]deltorphin II (10 or 20 micrograms) were significantly suppressed by i.c.v. pretreatment with delta-AS oligo but not MM oligo. The present results indicate that pretreatment with delta-AS oligo suppresses mouse locomotor hyperactivity produced by stimulation of delta 2-opioid receptors in the brain.
Insights
Intracerebroventricularly administered [D-Ala2]deltorphin II induced significant locomotor hyperactivity in mice. This effect was blocked by delta-opioid receptor antisense oligodeoxynucleotides, confirming delta 2-opioid receptor involvement in brain-mediated hyperactivity.
Area of Science:
- Neuroscience
- Pharmacology
- Behavioral Science
Background:
- Opioid receptors modulate various physiological processes, including motor activity.
- [D-Ala2]deltorphin II is a selective delta-opioid receptor agonist.
- Understanding the specific roles of opioid receptor subtypes is crucial for developing targeted therapeutics.
Purpose of the Study:
- To investigate the role of delta-opioid receptors in mediating locomotor hyperactivity induced by [D-Ala2]deltorphin II.
- To determine the involvement of delta 2-opioid receptors in the observed behavioral effects.
- To assess the efficacy of antisense oligodeoxynucleotides in blocking the action of [D-Ala2]deltorphin II.
Main Methods:
- Male ICR mice received intracerebroventricular (i.c.v.) injections.
- Locomotor activity was measured following administration of [D-Ala2]deltorphin II.
- Mice were pretreated with opioid receptor antagonists (naltriben, 7-benzylidene naltrexone, CTOP) or delta-opioid receptor antisense oligodeoxynucleotides (delta-AS oligo) and mismatch oligodeoxynucleotides (MM oligo).
Main Results:
- Intracerebroventricular [D-Ala2]deltorphin II (20 micrograms) induced marked locomotor hyperactivity.
- Pretreatment with naltriben (10 micrograms) suppressed hyperactivity, while 7-benzylidene naltrexone and CTOP did not.
- Pretreatment with delta-AS oligo (1 microgram) significantly suppressed [D-Ala2]deltorphin II-induced hyperactivity, whereas MM oligo did not.
Conclusions:
- The locomotor hyperactivity induced by [D-Ala2]deltorphin II is mediated by delta 2-opioid receptors in the brain.
- Antisense oligodeoxynucleotide technology can effectively suppress the behavioral effects mediated by specific opioid receptor subtypes.
- These findings contribute to understanding the central mechanisms of opioid receptor-mediated behaviors.