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Behavioural Brain Research 183 (2007) 4351 Research report

Summary: Behavioural Brain Research 183 (2007) 4351
Research report
Lateral hypothalamic orexin neurons are critically involved in
learning to associate an environment with morphine reward
Glenda C. Harris1, Mathieu Wimmer, Jovita F. Randall-Thompson2, Gary Aston-Jones
Department of Psychiatry, University of Pennsylvania, Translational Research Labs/3403, 125 S 31st Street, Philadelphia, PA 19104, United States
Received 1 March 2007; received in revised form 18 May 2007; accepted 21 May 2007
Available online 24 May 2007
Previously, we reported that lateral hypothalamic (LH) orexin neurons are stimulated in proportion to the preference shown for reward-associated
cues during conditioned place preference (CPP) testing. Here, we examine for the first time the role of these neurons in the acquisition of morphine
CPP. Results show that LH orexin neurons, but not those in the perifornical area (PFA), are stimulated during conditioning when morphine is given
in a novel drug-paired environment (CPP compartment) but not when given in the home cage, nor when saline was given in the CPP environment.
Furthermore, bilateral excitotoxic lesions of the LH orexin area completely blocked the acquisition of morphine CPP. Lesions that spared LH orexin
neurons had no effect. Orexin neurons in the LH project to the ventral tegmental area (VTA), an area important in the acquisition of morphine CPP.
Therefore, we investigated the importance of the LH orexin connection to the VTA in the acquisition of a morphine CPP using a disconnection
technique involving a unilateral excitotoxic lesion of LH orexin neurons and contralateral blockade of VTA orexin receptors. Results indicated
that a unilateral LH orexin lesion together with a microinjection of the orexin A antagonist (SB 334867) into the contralateral VTA prior to each
morphine-pairing session was sufficient to block the development of a morphine CPP. Either of these treatments by themselves was not sufficient
to block CPP development. These results demonstrate the importance of LH orexin neurons and their projections to the VTA in the formation of


Source: Aston-Jones, Gary - Department of Neurosciences, Medical University of South Carolina


Collections: Biology and Medicine