Obesity and drug addiction, both a result of aberrant motivated behavior, are growing problems in western society. Increased dopamine neurotransmission occurs with both drug-seeking and ingestive behaviors and has been linked to effort related functions. Hypocretin/orexin (Hcrt/ox) neurons have long been known to mediate arousal and feeding. Over the last 5 years, hcrt/ox has been demonstrated to play a novel role in mediating a variety of reward-seeking behaviors and can modulate the activity and output of dopamine neurons. Here, we propose that hcrt/ox action on mesolimbic dopamine circuitry serves to promote effort to obtain highly salient natural or drug rewards.
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