Joshua L Haight1,2, Paolo Campus3, Cristina E Maria-Rios1, Allison M Johnson4, Marin S Klumpner5, Brittany N Kuhn1,6, Ignacio R Covelo5,7, Jonathan D Morrow1,5, Shelly B Flagel8,9,10,11. 1. Neuroscience Graduate Program, University of Michigan, 4137 Undergraduate Science Building, 204 Washtenaw Avenue, Ann Arbor, MI, 48109, USA. 2. Department of Psychology, Quinnipiac University, 275 Mt Carmel Avenue, Hamden, CT, 06518, USA. 3. Michigan Neuroscience Institute, University of Michigan, 205 Zina Pitcher Place, Ann Arbor, MI, 48109, USA. 4. Undergraduate Program in Neuroscience, University of Michigan, 1140 Undergraduate Science Building, 204 Washtenaw Avenue, Ann Arbor, MI, 48109, USA. 5. Department of Psychiatry, University of Michigan, 4250 Plymouth Road, Ann Arbor, MI, 48105, USA. 6. Department of Neuroscience, Medical University of South Carolina, Basic Science Building, 173 Ashley Avenue, Room 403, Charleston, SC, 29425, USA. 7. Department of Psychology, University of Wisconsin-Parkside, 900 Wood Road, Kenosha, WI, 53144, USA. 8. Neuroscience Graduate Program, University of Michigan, 4137 Undergraduate Science Building, 204 Washtenaw Avenue, Ann Arbor, MI, 48109, USA. sflagel@umich.edu. 9. Michigan Neuroscience Institute, University of Michigan, 205 Zina Pitcher Place, Ann Arbor, MI, 48109, USA. sflagel@umich.edu. 10. Undergraduate Program in Neuroscience, University of Michigan, 1140 Undergraduate Science Building, 204 Washtenaw Avenue, Ann Arbor, MI, 48109, USA. sflagel@umich.edu. 11. Department of Psychiatry, University of Michigan, 4250 Plymouth Road, Ann Arbor, MI, 48105, USA. sflagel@umich.edu.
Abstract
RATIONALE: Prior research suggests that the neural pathway from the lateral hypothalamic area (LHA) to the paraventricular nucleus of the thalamus (PVT) mediates the attribution of incentive salience to Pavlovian reward cues. However, a causal role for the LHA and the neurotransmitters involved have not been demonstrated in this regard. OBJECTIVES: To examine (1) the role of LHA in the acquisition of Pavlovian conditioned approach (PavCA) behaviors, and (2) the role of PVT orexin 1 receptors (OX1r) and orexin 2 receptors (OX2r) in the expression of PavCA behaviors and conditioned reinforcement. METHODS: Rats received excitotoxic lesions of the LHA prior to Pavlovian training. A separate cohort of rats characterized as sign-trackers (STs) or goal-trackers (GTs) received the OX1r antagonist SB-334867, or the OX2r antagonist TCS-OX2-29, into the PVT, to assess their effects on the expression of PavCA behavior and on the conditioned reinforcing properties of a Pavlovian reward cue. RESULTS: LHA lesions attenuated the development of sign-tracking behavior. Administration of either the OX1r or OX2r antagonist into the PVT reduced sign-tracking behavior in STs. Further, OX2r antagonism reduced the conditioned reinforcing properties of a Pavlovian reward cue in STs. CONCLUSIONS: The LHA is necessary for the development of sign-tracking behavior; and blockade of orexin signaling in the PVT attenuates the expression of sign-tracking behavior and the conditioned reinforcing properties of a Pavlovian reward cue. Together, these data suggest that LHA orexin inputs to the PVT are a key component of the circuitry that encodes the incentive motivational value of reward cues.
RATIONALE: Prior research suggests that the neural pathway from the lateral hypothalamic area (LHA) to the paraventricular nucleus of the thalamus (PVT) mediates the attribution of incentive salience to Pavlovian reward cues. However, a causal role for the LHA and the neurotransmitters involved have not been demonstrated in this regard. OBJECTIVES: To examine (1) the role of LHA in the acquisition of Pavlovian conditioned approach (PavCA) behaviors, and (2) the role of PVT orexin 1 receptors (OX1r) and orexin 2 receptors (OX2r) in the expression of PavCA behaviors and conditioned reinforcement. METHODS:Rats received excitotoxic lesions of the LHA prior to Pavlovian training. A separate cohort of rats characterized as sign-trackers (STs) or goal-trackers (GTs) received the OX1r antagonist SB-334867, or the OX2r antagonist TCS-OX2-29, into the PVT, to assess their effects on the expression of PavCA behavior and on the conditioned reinforcing properties of a Pavlovian reward cue. RESULTS: LHA lesions attenuated the development of sign-tracking behavior. Administration of either the OX1r or OX2r antagonist into the PVT reduced sign-tracking behavior in STs. Further, OX2r antagonism reduced the conditioned reinforcing properties of a Pavlovian reward cue in STs. CONCLUSIONS: The LHA is necessary for the development of sign-tracking behavior; and blockade of orexin signaling in the PVT attenuates the expression of sign-tracking behavior and the conditioned reinforcing properties of a Pavlovian reward cue. Together, these data suggest that LHA orexin inputs to the PVT are a key component of the circuitry that encodes the incentive motivational value of reward cues.
Entities:
Keywords:
Incentive salience; Lateral hypothalamus; Orexin/hypocretin; Paraventricular nucleus of the thalamus; Sign-tracking
Authors: James M Otis; ManHua Zhu; Vijay M K Namboodiri; Cory A Cook; Oksana Kosyk; Ana M Matan; Rose Ying; Yoshiko Hashikawa; Koichi Hashikawa; Ivan Trujillo-Pisanty; Jiami Guo; Randall L Ung; Jose Rodriguez-Romaguera; E S Anton; Garret D Stuber Journal: Neuron Date: 2019-06-10 Impact factor: 17.173
Authors: Brittany N Kuhn; Marin S Klumpner; Ignacio R Covelo; Paolo Campus; Shelly B Flagel Journal: Psychopharmacology (Berl) Date: 2017-12-28 Impact factor: 4.530