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D3 receptor knockdown through antisense oligonucleotide administration supports its inhibitory role in locomotion
L B Menalled1, G Dziewczapolski, M C Garcia
1Instituto de Investigaciones Farmacológicas-CONICET, Buenos Aires, Argentina.
Abstract:
To study the specific contribution of the D3 dopamine receptor in the generation of locomotor activity, total or partially dopamine-depleted rats were pretreated with an antisense oligodeoxynucleotide for the D3 receptor (D3R-as) and locomotor activity induced by apomorphine was measured. A 35.7% increase in locomotor activity was seen in the totally dopamine-depleted rats pretreated with the D3R-as, whereas the same antisense, caused a significantly greater increase in the locomotor response (95%) in the partially dopamine-depleted rats compared with control groups (pretreated with a control oligodeoxynucleotide or vehicle). In situ autoradiography for D3 receptors showed a 27% fall in the density of D3 receptors in the islands of Calleja compared with control animals. Our results seem to confirm that D3 receptors exert an inhibitory effect on locomotor activity, through the stimulation of both pre- and postsynaptic components.
Insights
The D3 dopamine receptor (D3R) inhibits locomotor activity. Blocking D3R with antisense oligodeoxynucleotides significantly increased movement in rats, especially those with partial dopamine depletion.
Area of Science:
- Neuroscience
- Pharmacology
- Behavioral Science
Background:
- Dopamine receptors play a crucial role in regulating motor functions.
- The specific role of the D3 dopamine receptor (D3R) in locomotor activity remains to be fully elucidated.
- Understanding D3R's function is vital for developing treatments for movement disorders.
Purpose of the Study:
- To investigate the precise contribution of the D3 dopamine receptor to the generation of locomotor activity.
- To determine if D3R exerts an inhibitory or facilitatory effect on motor behavior.
Main Methods:
- Rats with total or partial dopamine depletion were pretreated with a D3 receptor-specific antisense oligodeoxynucleotide (D3R-as).
- Locomotor activity was measured after apomorphine administration.
- In situ autoradiography was used to quantify D3 receptor density in specific brain regions.
Main Results:
- D3R-as treatment significantly increased apomorphine-induced locomotor activity in both totally (35.7%) and partially (95%) dopamine-depleted rats compared to controls.
- Partially dopamine-depleted rats showed a markedly greater increase in locomotor response after D3R-as treatment.
- A 27% reduction in D3 receptor density was observed in the islands of Calleja in D3R-as treated animals.
Conclusions:
- D3 dopamine receptors exert an inhibitory influence on locomotor activity.
- This inhibitory effect appears to involve both presynaptic and postsynaptic mechanisms.
- Targeting D3 receptors may offer therapeutic potential for modulating motor behavior.