dopamine receptor agonists and operant behavior

Bill Skaggs bill at
Sat Sep 9 11:39:46 EST 1995

 mglinws at (MGLinWS) writes:

   > Does anyone know of any studies, published or unpublished, that have
   > described the effects of specific agonists of the dopamine D2 receptor,
   > such as quinpirole, on operant behavior ?  What about blocking these
   > effects with a specific antagonist, such as raclopride or eticlopride ? 
   > (I have searched Medline and not found much.)  

I don't have a collection of references, but the story as I understand
it is that rewarding effects require activation of both D1 and D2
receptors in the nucleus accumbens.  Thus, specific D2 agonists are
only minimally rewarding at best.  (Cocaine and amphetamine work by
increasing the amount of dopamine at the synapses, thereby activating
both D1 and D2 receptors equally.)  In large doses, D2 agonists
actually make you throw up, by activating dopaminergic cells in the
brain's poison-detection system.  On the other hand, specific D2
antagonists, such as neuroleptics, are highly effective in reducing
reward -- which is probably a major reason why schizophrenics hate
them so much.

The requirement for both D1 and D2 activation makes a lot of sense
when you think about it.  Short-circuiting of the brain's reward
system is a functional disaster, because it leads to drug-seeking
behavior instead of adaptive behavior.  The requirement that two types
of receptor be simultaneously activated dramatically reduces the
possibilities for short-circuiting the system -- essentially the only
way to do it is either to use a cocktail of D1 and D2 agonists or else
to increase the level of dopamine itself.

	-- Bill

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