Drug info - How cocaine gives its hyperactive high

[jholmes800]

Washington, Dec 7(ANI): That cocaine, a stimulating alkaloid crushed out of the leaves of the coca plant-increases euphoria and energy as well as triggers off a mind-killing addiction in humans, is well known. But researchers have now for the first time shed light on how it causes its effect on the brain, by tracing the hyperactive high of cocaine to interactions between two types of receiving stations in neurons for nerve signals from their neighbours John Wang, of the University of Missouri, Kansas City School of Medicine, and his colleagues who conducted studies in rats found that when the animals received cocaine, a component of a receptor for the neurotransmitter dopamine tends to grab onto a component of a receptor for glutamate. Neurons trigger nerve impulses in their neighbours by launching bursts of chemicals called neurotransmitters at them. The neurotransmitters activate protein receptors on the receiving neurons, which induce the nerve impulses in the receiving cell. These receptors also adjust themselves in complex ways to alter the sensitivity of the receiving neuron to stimulation. The researchers found that in the striatum of the brain the dopamine receptors known as D2 interfered with the normal function of some glutamate receptors--known as NR2B--by blocking their activation. The researchers also analysed whether this interaction between D2R and NR2B affected the rats' behavioural response to cocaine-specifically the hyperactivity and intensive sniffing and biting the drug elicits in the animals. They found that drugs that either activated the D2R subunit or inactivated the NR2B subunit tended to enhance such behavioural responses to cocaine. "These results provide strong evidence supporting a critical role of the D2R-NR2B interaction in mediating cocaine's effect on [kinase binding and phosphorylation] and in constructing a full-scale motor response to cocaine," concluded the researchers. The study is published in the December 7 issue of the journal Neuron. (ANI)

http://in.news.yahoo.com/061207/139/6a3ec.html

[Jatelka]

And if any SWIY has access to the full paper it would be VERY interesting to have it in the archive!

[dolphinsnow18]

I dont get it. Hasnt neurotransmtter and receptor blocking from drugs been known to science for many years as the cause of euphoria in the brain? What is the article telling us that we dont already know? What am I missing here?

[Bajeda]

Believe this is the article being talked about, though I don't have access to the full thing as of yet. Need medline for that I think (grrrrr).


Title: Modulation of D2R-NR2B Interactions in Response to Cocaine.
Author: Liu, Xian-Yu
Add.Author / Editor: Wang, Min Zhang, Guo-Chi Lan, Hong-Xiang Chu, Xiang-Ping Mao, Li-Min Fibuch, Eugene E Li, Ming-Hua Parelkar, Nikhil K
Citation: Neuron. Volume: 52, Issue: 5, Date: 2006 12 05, Pages: 897-909 Year: 2006
Abstract: Dopamine-glutamate interactions in the neostriatum determine psychostimulant action, but the underlying molecular mechanisms remain elusive. Here we found that dopamine stimulation by cocaine enhances a heteroreceptor complex formation between dopamine D2 receptors (D2R) and NMDA receptor NR2B subunits in the neostriatum in vivo. The D2R-NR2B interaction is direct and occurs in the confined postsynaptic density microdomain of excitatory synapses. The enhanced D2R-NR2B interaction disrupts the association of Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) with NR2B, reduces NR2B phosphorylation at a CaMKII-sensitive site (Ser1303), and inhibits NMDA receptor-mediated currents in medium-sized striatal neurons. Furthermore, the regulated D2R-NR2B interaction is critical for constructing behavioral responsiveness to cocaine. Our findings here uncover a direct and dynamic D2R-NR2B interaction in striatal neurons in vivo. This type of dopamine-glutamate integration at the receptor level may be responsible for synergistically inhibiting the D2R-mediated circuits in the basal ganglia and fulfilling the stimulative effect of psychostimulants.