Poster abstracts

Poster number 81 submitted by Keerthi Thirtamara Rajamani

Dopamine D5 receptors in the nucleus accumbens are involved in mediating cocaine induced locomotor activity

Keerthi Thirtamara Rajamani (Pharmacology, Ohio State University), Howard Gu (Pharmacology, Ohio State University)

Abstract:
Dopamine D1-like (D1R and D5R) receptors are expressed to varying degrees in the striatum, an important brain region that mediates cocaine’s rewarding and reinforcing effects. It is also known that D1-like receptors are essential for regulating dopamine mediated motor activity. However, there is an incomplete understanding of contribution of these receptors (independent of each other) within specific brain regions and how they modulate these behaviors. The aim of this study was to delineate their roles on an individual basis in mediating actions of cocaine induced dopamine within the striatum. Adeno associated viral vector containing either short hairpin RNA’s against D1R (D1shR) or D5R (D5shR) were injected in the lateral nucleus accumbens (1ul per hemisphere, 1x10^12 vgu/ul). Following three weeks of recovery, basal locomotion and cocaine induced locomotor activity was measured at 1.0mg, 2.5mg, 5mg and 10mg. Immunohistochemistry was performed on all animals to identify the site and spread of viral injection. Knockdown of D5R in the nucleus accumbens resulted in an increase in basal locomotion. No effect was observed in D1R knockdown animals in the same region. At 1.0mgkg and 2.5mgkg dose of cocaine, control animals exhibit locomotor suppression relative to saline, with no difference observed at 5mgkg. However, D5shR injected animals display locomotor suppression at 1.0mgkg and a marked stimulation to 5mgkg cocaine, with no difference observed at 2.5mgkg cocaine. No effect of cocaine was observed at all three doses, in D1shR injected animals. Thus, D5 receptors may play an inhibitory role in mediating locomotor activity and at lower doses of cocaine may shift the balance of cocaine’s locomotor suppressing/stimulating effects. In conclusion, we show that D5R in the nucleus accumbens may be essential for regulating basal locomotor activity and in the presence of cocaine may serve to maintain a balance between its suppressing and stimulating effects.

References:
1. Surmeier DJ, Song WJ, Yan Z., Coordinated expression of dopamine receptors in neostriatal medium spiny neurons.J Neurosci. 1996 Oct 15;16(20):6579-91.
2. Khan ZU, Gutiérrez A, Martín R, Peñafiel A, Rivera A, de la Calle A. Dopamine D5 receptors of rat and human brain. Neuroscience. 2000;100(4):689-99.
3. Meyer ME, Cottrell GA, Van Hartesveldt C, Potter TJ. Effects of dopamine D1 antagonists SCH23390 and SK&F83566 on locomotor activities in rats.Pharmacol Biochem Behav. 1993 Feb;44(2):429-32.

Keywords: Dopamine D5 receptors, Nucleus accumbens, Cocaine