Abstract
The lateral preoptic area (LPO) is a hypothalamic region whose function has been largely unexplored. Its direct and indirect projections to the ventral tegmental area (VTA) suggest that the LPO could modulate the activity of the VTA and the reward-related behaviors that the VTA underlies. We examined the role of the LPO on reward taking and seeking using operant self-administration of cocaine or sucrose. Rats were trained to self-administer cocaine or sucrose and then subjected to extinction, whereby responding was no longer reinforced. We tested if stimulating the LPO pharmacologically with bicuculline or chemogenetically with Designer Receptors Exclusively Activated by Designer Drugs (DREADDs) modifies self-administration and/or seeking. In another set of experiments, we tested if manipulating the LPO influences cocaine self-administration during and after punishment. To examine the functional connectivity between the LPO and VTA, we used in vivo electrophysiology recordings in anesthetized rats. We tested if stimulating the LPO modifies the activity of GABA and dopamine neurons of the VTA. We found that stimulating the LPO reinstated cocaine and sucrose seeking behavior but had no effect on reward intake. Furthermore, both stimulating and inhibiting the LPO prevented the sustained reduction in cocaine intake seen after punishment. Finally, stimulating the LPO inhibited the activity of VTA GABA neurons while enhancing that of VTA dopamine neurons. These findings indicate that the LPO has the capacity to drive reward seeking, modulate sustained reductions in self-administration following punishment, and regulate the activity of VTA neurons. Taken together, these findings implicate the LPO as a previously overlooked member of the reward circuit.
Highlights
The lateral preoptic area (LPO) is an anterior hypothalamic brain region whose function has been largely unexplored
We examined the role of the LPO in reward behavior using operant self-administration of cocaine or sucrose
We determined if pharmacological stimulation of the LPO modulates cocaine self-administration or extinguished cocaine seeking behavior using operant conditioning (Figure 1)
Summary
The lateral preoptic area (LPO) is an anterior hypothalamic brain region whose function has been largely unexplored. The LPO projects to brain regions that influence the activity of VTA neurons, including, but not limited to, the lateral habenula (Mok and Mogenson, 1972; Kowski et al, 2008; Yetnikoff et al, 2015; Barker et al, 2017), rostromedial tegmental nucleus (Jhou et al, 2009; Yetnikoff et al, 2015), and dorsal raphe (Peyron et al, 1998; Ogawa et al, 2014) Taken together, these studies led us to postulate that the LPO modulates VTA activity and reward behavior
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
