We've updated our Privacy Policy to make it clearer how we use your personal data.

We use cookies to provide you with a better experience. You can read our Cookie Policy here.

Advertisement
Dopamine signaling pathway that controls cocaine reward in mice identified
News

Dopamine signaling pathway that controls cocaine reward in mice identified

Dopamine signaling pathway that controls cocaine reward in mice identified
News

Dopamine signaling pathway that controls cocaine reward in mice identified

Read time:
 

Want a FREE PDF version of This News Story?

Complete the form below and we will email you a PDF version of "Dopamine signaling pathway that controls cocaine reward in mice identified "

First Name*
Last Name*
Email Address*
Country*
Company Type*
Job Function*
Would you like to receive further email communication from Technology Networks?

Technology Networks Ltd. needs the contact information you provide to us to contact you about our products and services. You may unsubscribe from these communications at any time. For information on how to unsubscribe, as well as our privacy practices and commitment to protecting your privacy, check out our Privacy Policy

Researchers have thus far been unable to define how dopamine influences cocaine reward. A recent report published in Neuron has shown that cocaine administration increases dopamine levels in the striatum, activating a signaling pathway that was previously unknown.


Dopamine activates a protein called PKA in striatal neurons, which activates many additional substrates to regulate neuronal excitability and control behavior. However, the identities of these PKA substrates are not known. Recently, a research team at Nagoya University has uncovered the answers.


See Also: Sensation-seeking, reward sensitivity and early cannabis use


"We stimulated PKA in mouse brain slices to activate these unknown substrates," explains corresponding author Kozo Kaibuchi of the University of Nagoya's Department of Cell Pharmacology. His research team was able to extract these activated proteins from brain slices and identify them. "Using this screening approach, we identified more than 100 candidate substrates of PKA," continues Kaibuchi.


One of these novel candidates was Rasgrp2, a protein that is highly expressed in striatal neurons. Rasgrp2 positively regulates another protein called Rap1 and the authors were intrigued to find out whether Rap1 was activated by Rasgrp2 in striatal neurons. Through a range of experiments, the Nagoya research group found the answer; they demonstrated that cocaine treatment increased the phosphorylation of Rasgrp2 by PKA, which in turn activated Rap1 in striatal neurons.


"We speculated that the Rap1 pathway is involved in the regulation of neuronal functions by dopamine," says lead author Taku Nagai at the university's Department of Neuropsychcopharmacology. By measuring neuronal activity directly in mouse brain slices, Nagai and colleagues discovered that activated Rap1 can increase the activity of dopaminergic neurons in the striatum. In addition, the rewarding effects of cocaine were higher when Rap1 was activated in mouse brains.


Learn More: People with opioid dependence in recovery show 're-regulation' of reward systems


"When dopamine levels increase due to cocaine administration, striatal neurons become more excitable, resulting in enhanced responses to excitatory input from other brain regions," explains Nagai. "This increases the sensitivity of mice to cocaine reward."


Many of the 100 candidate PKA substrates identified were previously unknown as components of dopamine signaling. Therefore in the future, these findings will significantly contribute to our understanding of the different roles of dopamine in many brain functions.


Note: Material may have been edited for length and content. For further information, please contact the cited source.

Nagoya University


Publication

Nagai T et al. Phosphoproteomics of the Dopamine Pathway Enables Discovery of Rap1 Activation as a Reward Signal In Vivo.  Neuron, Published February 3 2016. doi: 10.1016/j.neuron.2015.12.019


Advertisement