Food Intake And Locomotor Activity Effects Induced By Opioid Stimulation Within The Prefrontal Cortex Are Selectively Mediated By Glutamate Receptors In The Lateral Hypothalamus and Nucleus Accumbens Shell

Feeding is a complex biological function mediated by many brain structures.  Recently, we discovered that stimulating opioid receptors within the prefrontal cortex (PFC) with the drug DAMGO induces over-eating in free feeding and hungry rats.  This phenomenon is accompanied by hyperactivity and a 'fragmented' feeding profile.  Informed by electrophysiological  findings in the literature, we hypothesize that intra-PFC DAMGO leads to pyramidal cell activation and subsequent glutamatergic output to downstream feeding-related sites.  To test this, we performed double cannulation surgeries in two groups of rats targeting the PFC and either the lateral hypothalamus (LH) or accumbens shell (AcbSh).  Animals in one group received infusions of either saline or DAMGO in the PFC and a glutamate receptor antagonist, AP-5, in the LH. Because it has been shown previously that AP-5 has no effect on feeding when administered into the AcbSh, animals in the other group received infusions of either saline or DAMGO in the PFC and CNQX, another glutamate receptor antagonist, in the AcbSh. Animals were then placed in testing cages and their feeding behavior was examined.  We discovered differential contributions of glutamate receptors between the LH and AcbSh on food intake and locomotor activity.  Blocking glutamate receptors within the LH selectively suppressed DAMGO-induced increases in food intake but left locomotor activity unaffected.  Conversely, blocking glutamate receptors within the AcbSh significantly suppressed DAMGO-induced increases in locomotor activity but was simply additive on food intake.  These data support our hypothesis and begin to delineate the neural circuitry underlying the intra-PFC DAMGO effect.