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Receptor-selective opioid peptides fail to affect behavioral responses induced by a low dose of apomorphine in the
M Ukai1, T Toyoshi, T Kameyama
1Department of Chemical Pharmacology, Faculty of Pharmaceutical Sciences, Meijo University, Nagoya, Japan.
Abstract:
The effects of intracerebroventricular injections of the mu-selective opioid agonist DAMGO ([D-Ala2,NMePhe4,Gly-ol]enkephalin), the kappa-selective opioid agonist dynorphin A-(1-13), and the delta-selective opioid agonist DPLPE ([D-Pen2,L-Pen5]enkephalin) on the decrease in different behavioral responses induced by a low dose of apomorphine (0.03 mg/kg) were investigated in the mouse. A low dose (0.03 mg/kg) of apomorphine produced a marked decrease in behavioral responses such as circling and rearing. Although the dopamine D1 antagonist SCH 23390 (0.01 and 0.03 mg/kg) did not influence behavior induced by apomorphine (0.03 mg/kg), the dopamine D2 antagonist sulpiride (3.0 mg/kg) reversed the decrease in circling and rearing behavior induced by apomorphine, suggesting that the effects of apomorphine on circling and rearing are mediated through dopamine D2 autoreceptors. DAMGO (0.003 or 0.01 microgram), dynorphin A-(1-13) (3.0 or 10.0 micrograms), or DPLPE (0.3 and 1.0 microgram) had no significant effects on the apomorphine-induced decrease in circling and rearing behavior. These in vivo results suggest that opioid peptides selective for receptor types fail to influence drug effects mediated by dopamine D2 autoreceptors.
Insights
Opioid peptides did not alter apomorphine-induced behaviors in mice, suggesting these effects are mediated by dopamine D2 autoreceptors, not opioid receptors. This research explores dopamine and opioid interactions in mouse behavior.
Area of Science:
- Neuropharmacology
- Behavioral Neuroscience
- Opioid and Dopamine Receptor Systems
Background:
- Apomorphine, a dopamine receptor agonist, induces behavioral changes like circling and rearing in mice.
- Dopamine D2 autoreceptors are implicated in mediating apomorphine's effects on these behaviors.
- The interaction between opioid systems and dopamine D2 autoreceptors in modulating these behaviors is not fully understood.
Purpose of the Study:
- To investigate the influence of selective mu, kappa, and delta opioid agonists on apomorphine-induced behavioral changes in mice.
- To determine if opioid receptor activation can modulate behaviors mediated by dopamine D2 autoreceptors.
Main Methods:
- Intracerebroventricular injections of selective opioid agonists: DAMGO (mu), dynorphin A-(1-13) (kappa), and DPLPE (delta) in mice.
- Administration of a low dose of apomorphine (0.03 mg/kg) to induce circling and rearing behaviors.
- Assessment of the effects of opioid agonists and dopamine antagonists (SCH 23390 and sulpiride) on apomorphine-induced behaviors.
Main Results:
- Apomorphine (0.03 mg/kg) significantly decreased circling and rearing behaviors.
- The dopamine D2 antagonist sulpiride reversed the apomorphine-induced decrease in these behaviors, confirming D2 autoreceptor mediation.
- Selective opioid agonists (DAMGO, dynorphin A-(1-13), DPLPE) did not significantly affect the apomorphine-induced decrease in circling and rearing.
Conclusions:
- Opioid peptides selective for mu, kappa, or delta receptors do not influence behaviors mediated by dopamine D2 autoreceptors.
- These findings suggest a dissociation between opioid receptor pathways and dopamine D2 autoreceptor-mediated behaviors in the studied mouse model.
- Further research is needed to elucidate the complex interplay between different neurotransmitter systems in regulating complex behaviors.