PACAP induces increased excitability in D1- and D2-expressing nucleus accumbens medium spiny neurons
Addgene #100833-AAV9
- Data Submitted By
- Sonia Ortega-Tinoco
- Lab Name
- Salvador Hernández-López, Departamento de Fisiología, Facultad de Medicina, Universidad Nacional Autónoma de México (UNAM)
- Submission Date
- September 08, 2025
- Publication Date
- October 17, 2025 (modified October 17, 2025)
- Funding
- CONAHCyT 1102522
- Abstract
- One of the main eating disorders associated with overweight and obesity is binge eating disorder. Binge eating is characterized by excessive consumption of high-calorie foods over a short period of time, approximately 2 hours. The nucleus accumbens (NAc) plays a key role in modulating the hedonic value of high-calorie foods, commonly referred to as palatable foods. Specific subregions of the shell portion of the NAc (NAcSh), known as hedonic hot spots, may play an important role in the motivational aspect of food consumption. Previous work has shown that the pituitary adenylate cyclase-activating polypeptide (PACAP) injected into the NAc reduces palatable food intake, suggesting that this peptide could be a potential tool for treating binge eating. However, the mechanisms of action of PACAP on the NAc are poorly understood. Here, we used whole-cell recording and calcium imaging techniques in NAcSh brain slices from D1-Cre and A2A-Cre mice to investigate PACAP modulation of medium spiny neuron (MSN) activity. We found that PACAP administration increased the firing rate of D1- and D2- expressing MSNs. In addition, in a binge-eating mouse model, nasal PACAP reduced binge-eating behavior.
Image attribution: Sonia Ortega-Tinoco
Image attribution: Sonia Ortega-Tinoco
Image attribution: Sonia Ortega-Tinoco
This report is made available under the Creative Commons Attribution 4.0 International License.
- Vector Used
-
pAAV.Syn.Flex.GCaMP6f.WPRE.SV40
Addgene #100833-AAV9
Virus & Injection
Virus
- Virus Name
- pAAV.Syn.Flex.GCaMP6f.WPRE.SV40
- Serotype
- AAV9
- Source
- Addgene
- Catalog Number
- 100833-AAV9
- Promoter
- Synapsin
- Cargo Type
- Biosensor
- Injection Titer / Dose
- Bilateral injections of 0.6 μL of 100833-AAV9: pAAV.Syn.Flex.GCaMP6f.WPRE.SV40 were administered into the nucleus accumbens shell (NAcSh) using a 30G dental needle attached to a microinjection system, at a rate of 0.1 μL/min.
- Injection Volume
- 0.6 μL
- Injection Rate
- 0.1 μL/min
- Injector Material
- 30G dental needle
- Injection Site / Route
- Nucleus accumbens shell (NAcSh) at stereotaxic coordinates relative to bregma: AP +1.1 mm, ML ±1.1 mm, DV -5.2 mm.
Other Details
- Species
- Mouse
- Strain or Cell Line
- C57BL/6J, D1-Cre mice (Drd1a-Cre), and D2-Cre mice (Adora2a-Cre)
- Source
- D1-Cre mice: Jax stock #030329; D2-Cre mice: MMRRC_031168-UCD
- Age at Injection
- 30 days
- Sex
- Male
- Time After Injection
- 18–21 days
- Detection Method
- Whole-field fluorescence
- Assay & Results
- The image field was visualized under a microscope and the field size was 280 ×260 μm size. The tissue was stimulated with light pulses (488 nm wavelength, 15–25 ms exposure time) using a LED lamp (Lambda HpX L5, Sutter Instruments) connected to the microscope via fiber optics. Image sequences were acquired at a frequency of 4 frames/s (250 ms/frame) by using a digital camera (Cool SNAP MYO, Photometrics)
- Tips & Comments
- Please see the original publication for more details: Ortega-Tinoco, S., Padilla-Orozco, M., Hernández-Vázquez, F., Garduño, J., Mondragón-García, A., Ramírez-Sánchez, E., Bargas, J., & Hernández-López, S. (2025). PACAP induces increased excitability in D1- and D2-expressing nucleus accumbens medium spiny neurons. Brain research bulletin, 224, 111323. https://doi.org/10.1016/j.brainresbull.2025.111323