William Norbey Sanchez Luna, Ph.D.

@article{pmid40930333,

title = {PROGESTERONE ATTENUATES THE EFFECTS OF COCAINE ON HYPERMOBILITY AND DOPAMINERGIC TRANSMISSION IN THE NUCLEUS ACCUMBENS},

author = {William N Sánchez and José A Pochapski and A Leslie Morrow and Roberto Andreatini and Donita L Robinson and Rainer K W Schwarting and Sergi Ferré and Claudio Da Cunha},

url = {https://pubmed.ncbi.nlm.nih.gov/40930333/},

doi = {10.1016/j.neuropharm.2025.110680},

issn = {1873-7064},

year  = {2025},

date = {2025-09-01},

urldate = {2025-09-01},

journal = {Neuropharmacology},

pages = {110680},

abstract = {Currently there is no pharmacological treatment for cocaine use disorder. Previous studies have shown that progesterone can mitigate the behavioral effects induced by cocaine in both animal models and humans. However, the underlying mechanisms through which progesterone exerts this effect remain poorly understood. While it was already known that exogenous progesterone can decrease dopamine release in the nucleus accumbens (NAc) of male rats, it remains unclear whether progesterone could also reduce the cocaine-induced increase in extracellular dopamine levels. Here we evaluated if exogenous progesterone could reduce cocaine-induced increases in mobility, locomotion, ultrasonic vocalizations and electrically-evoked change in dopamine levels in the NAc of adult male and female rats. Progesterone decreased electrically-evoked dopamine levels, locomotion and mobility in both males and females, being more effective in female rats. Moreover, progesterone attenuated the cocaine-induced increase in the electrically-evoked dopamine concentration in the NAc. Rats exhibited stimulant euphoric-like and rewarding effects of cocaine through increased mobility, locomotion, and 50-kHz ultrasonic vocalization (USV) calls. We also found that progesterone attenuates these effects of cocaine in female, but not male, rats, suggesting that progesterone may dampen the rewarding, euphoric, and psychostimulant effects of cocaine, but with sex differences.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid40784438,

title = {Distinctive biochemical properties of the μ-opioid receptor-corticotropin- releasing factor CRF receptor heterotetramer},

author = {William N Sanchez and Estefanía Moreno and Marc Ciruela-Jardí and Nil Casajuana-Martín and Anne Yauch and Ning-Sheng Cai and Cesar Quiroz and Ya Gin Chang and Vicent Casadó and Leonardo Pardo and Leigh D Plant and Sergi Ferré},

url = {https://pubmed.ncbi.nlm.nih.gov/40784438/},

doi = {10.1016/j.phrs.2025.107904},

issn = {1096-1186},

year  = {2025},

date = {2025-09-01},

urldate = {2025-09-01},

journal = {Pharmacol Res},

volume = {219},

pages = {107904},

abstract = {Heteromerization of Gs with Gi protein-coupled receptors has been suggested to be necessary to sustain the canonical Gi-Gs antagonistic interaction at adenylyl cyclase (AC). These heteromers have a tetrameric quaternary structure, composed by two homodimers each one coupled to its corresponding G protein. We describe the heterotetramer formed by the Gi-coupled μ-opioid receptor (MOR) and the Gs-coupled corticotropin releasing factor CRF receptor (CRFR), which also sustains a canonical interaction at AC and reciprocal allosteric interactions between MOR and CRFR ligands. In addition, we found that CRFR can also couple to Gq proteins in the MOR-CRFR heteromer, providing the frame for also canonical Gi-Gq antagonistic interactions that include other effectors, such as phospholipase C and its Ca -dependent signaling, and which control glutamate release in the central amygdala (CeA). The specific pharmacodynamic properties of the MOR-CRFR heteromer, including its sensitivity to S-methadone, as well as its localization in the CeA suggest it might represent a significant pharmacological target for the analgesic, antistressor and antidepressant effects of opioids and the hyperalgesia of opioid withdrawal.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid40692178,

title = {Dissection of Neurochemical Pathways Across Complexity and Scale},

author = {Alice Abbondanza and Nawon Kim and Ricardo A S Lima-Filho and Azin Amin and Roberta G Anversa and Felipe Borges Almeida and Pablo L Cardozo and Giovanna Carello-Collar and Emma V Carsana and Royhaan O Folarin and Sara Guerreiro and Olayemi K Ijomone and Sodiq K Lawal and Isadora Matias and Smart I Mbagwu and Sandra A Niño and Bolanle F Olabiyi and Sunday Y Olatunji and Tosin A Olasehinde and Waralee Ruankham and William N Sanchez and Carina Soares-Cunha and Paula A Soto and Jazmín Soto-Verdugo and Nathan R Strogulski and Weronika Tomaszewska and Cármen Vieira and Adriano Chaves-Filho and Michael A Cousin and Ago Rinken and Tyler J Wenzel},

url = {https://pubmed.ncbi.nlm.nih.gov/40692178/},

doi = {10.1111/jnc.70160},

issn = {1471-4159},

year  = {2025},

date = {2025-07-01},

urldate = {2025-07-01},

journal = {J Neurochem},

volume = {169},

number = {7},

pages = {e70160},

abstract = {The field of Neurochemistry spent decades trying to understand how the brain works, from nano to macroscale and across diverse species. Technological advancements over the years allowed researchers to better visualize and understand the cellular processes underpinning central nervous system (CNS) function. This review provides an overview of how novel models, and tools have allowed Neurochemistry researchers to investigate new and exciting research questions. We discuss the merits and demerits of different in vivo models (e.g., Caenorhabditis elegans, Drosophila melanogaster, Ratus norvegicus, and Mus musculus) as well as in vitro models (e.g., primary cells, induced pluripotent stem cells, and immortalized cells) to study Neurochemical events. We also discuss how these models can be paired with cutting-edge genetic manipulation (e.g., CRISPR-Cas9 and engineered viral vectors) and imaging techniques, such as super-resolution microscopy and new biosensors, to study cellular processes of the CNS. These technological advancements provide new insight into Neurochemical events in physiological and pathological contexts, paving the way for the development of new treatments (e.g., cell and gene therapies or small molecules) that aim to treat neurological disorders by reverting the CNS to its homeostatic state.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid38159887,

title = {Biperiden reverses the increase in 50-kHz ultrasonic vocalizations but not the increase in locomotor activity induced by cocaine},

author = {Thais C S Saldanha and William N Sanchez and Paola Palombo and Fábio C Cruz and José Carlos F Galduróz and Rainer K W Schwarting and Roberto Andreatini and Claudio da Cunha and José Augusto Pochapski},

url = {https://pubmed.ncbi.nlm.nih.gov/38159887/},

doi = {10.1016/j.bbr.2023.114841},

issn = {1872-7549},

year  = {2024},

date = {2024-03-01},

urldate = {2024-03-01},

journal = {Behav Brain Res},

volume = {461},

pages = {114841},

abstract = {Cocaine use disorder (CUD) is a worldwide public health problem, associated with severe psychosocial and economic impacts. Currently, no FDA-approved treatment is available for CUD. However, an emerging body of evidence from clinical and preclinical studies suggests that biperiden, an M1 muscarinic receptor antagonist, presents potential therapeutic use for CUD. These studies have suggested that biperiden may reduce the reinforcing effects of cocaine. It is well established that rodents emit 50-kHz ultrasonic vocalizations (USV) in response to natural rewards and stimulant drugs, including cocaine. Nonetheless, the effects of biperiden on the cocaine-induced increase of 50-kHz USV remains unknown. Here, we hypothesized that biperiden could antagonize the acute effects of cocaine administration on rat 50-kHz USV. To test this hypothesis, adult male Wistar rats were divided into four experimental groups: saline, 5 mg/kg biperiden, 10 mg/kg cocaine, and biperiden/cocaine (5 and 10 mg/kg, i.p., respectively). USV and locomotor activity were recorded in baseline and test sessions. As expected, cocaine administration significantly increased the number of 50-kHz USV. Biperiden administration effectively antagonized the increase in 50-kHz USV induced by cocaine. Cocaine administration also increased the emission of trill and mixed 50 kHz USV subtypes and this effect was antagonized by biperiden. Additionally, we showed that biperiden did not affect the cocaine-induced increase in locomotor activity, although biperiden administration per se increased locomotor activity. In conclusion, our findings indicate that administering biperiden acutely reduces the positive affective effects of cocaine, as demonstrated by its ability to inhibit the increase in 50-kHz USV.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid37952685,

title = {Forty-kHz ultrasonic vocalizations of rat pups predict adult behavior in the elevated plus-maze behavior but not the effect of cocaine on 50-kHz ultrasonic vocalizations},

author = {Nícolas Cordeiro and José Augusto Pochapski and William Sanchez Luna and Gabriel Baltazar and Rainer K Schwarting and Roberto Andreatini and Claudio Da Cunha},

url = {https://pubmed.ncbi.nlm.nih.gov/37952685/},

doi = {10.1016/j.bbr.2023.114759},

issn = {1872-7549},

year  = {2024},

date = {2024-02-01},

urldate = {2024-02-01},

journal = {Behav Brain Res},

volume = {458},

pages = {114759},

abstract = {Ultrasonic vocalizations (USV) are emitted by both young pups and adult rats to convey positive or negative emotional states. These USV manifestations are contingent on factors including developmental stage, situational requirements, and individual dispositions. Pups emit 40-kHz USV when separated from their mother and litter, which function to elicit maternal care. Conversely, adult rats can produce 50-kHz USV in response to stimuli that elicit reward-related states, including natural rewards, stimulant drugs, and reward-predictive stimuli. The present study aims to investigate whether pup 40-kHz USV can serve as predictors of behaviors related to positive or negative states in adult rats. Both male and female Wistar pups were initially tested on the 11th postnatal day and subsequently in adulthood. There was no significant difference in the number of 40-kHz ultrasonic vocalizations between male and female pups. However, cocaine elicited more 50-kHz USV and hyperactivity in adult females compared to males. Notably, cocaine increased the proportion of step and trill USV subtypes in both adult males and females. Interestingly, this effect of cocaine was stronger in females that were in the diestrus, compared to the estrus phase. In males, a significant positive correlation was found between pup 40-kHz USV and lower anxiety scores in adult male but not female rats tested on the elevated plus-maze test. Furthermore, no significant correlation was found between pup 40-kHz and adult 50-kHz USV in both males and females, whether in undrugged (saline) or in cocaine-treated rats. It is possible that the 40-kHz USV emitted by pups predicted reduced anxiety-like behavior only for male rats because they could elicit maternal care directed specifically to male pups. These findings suggest that 40-kHz USV can serve as an indicator of the emotional link between the rat mother and male pups. Indeed, this suggests that maternal care exerts a positive influence on the emotional state during adulthood.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid36037842,

title = {Pre-clinical evidence that methylphenidate increases motivation and/or reward preference to search for high value rewards},

author = {Laura N Pulido and Jose A Pochapski and Adam Sugi and Julie Y Esaki and Joao L Stresser and William N Sanchez and Gabriel Baltazar and David Levcik and Romulo Fuentes and Claudio Da Cunha},

url = {https://pubmed.ncbi.nlm.nih.gov/36037842/},

doi = {10.1016/j.bbr.2022.114065},

issn = {1872-7549},

year  = {2023},

date = {2023-02-01},

urldate = {2023-02-01},

journal = {Behav Brain Res},

volume = {437},

pages = {114065},

abstract = {Methylphenidate is a stimulant used to treat attention deficit and hyperactivity disorder (ADHD). In the last decade, illicit use of methylphenidate has increased among healthy young adults, who consume the drug under the assumption that it will improve cognitive performance. However, the studies that aimed to assess the methylphenidate effects on memory are not consistent. Here, we tested whether the effect of methylphenidate on a spatial memory task can be explained as a motivational and/or a reward effect. We tested the effects of acute and chronic i.p. administration of 0.3, 1 or 3 mg/kg of methylphenidate on motivation, learning and memory by using the 8-arm radial maze task. Adult male Wistar rats learned that 3 of the 8 arms of the maze were consistently baited with 1, 3, or 6 sucrose pellets, and the number of entries and reentries into reinforced and non-reinforced arms of the maze were scored. Neither acute nor chronic (20 days) methylphenidate treatment affected the number of entries in the non-baited arms. However, chronic, but not acute, 1-3 mg/kg methylphenidate increased the number of reentries in the higher reward arms, which suggests a motivational/rewarding effect rather than a working memory deficit. In agreement with this hypothesis, the methylphenidate treatment also decreased the approach latency to the higher reward arms, increased the approach latency to the low reward arm, and increased the time spent in the high, but not low, reward arm. These findings suggest that methylphenidate may act more as a motivational enhancer rather than a cognitive enhancer in healthy people.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid34389975,

title = {Diazepam attenuates the effects of cocaine on locomotion, 50-kHz ultrasonic vocalizations and phasic dopamine in the nucleus accumbens of rats},

author = {William N Sanchez and Jose A Pochapski and Leticia F Jessen and Marek Ellenberger and Rainer K Schwarting and Donita L Robinson and Roberto Andreatini and Claudio Da Cunha},

url = {https://pubmed.ncbi.nlm.nih.gov/34389975/},

doi = {10.1111/bph.15658},

issn = {1476-5381},

year  = {2021},

date = {2021-08-01},

urldate = {2021-08-01},

journal = {Br J Pharmacol},

abstract = {BACKGROUND AND PURPOSE: Currently, there is no effective drug to treat cocaine-use disorder, which affects millions of people worldwide. Benzodiazepines are potential therapeutic candidates, as microdialysis and voltammetry studies have shown that they can decrease dopamine concentrations in the nucleus accumbens of rodents and block the increase in dopamine levels and appetitive 50-kHz ultrasonic vocalizations (USVs) induced by amphetamine in rats.



EXPERIMENTAL APPROACH: Here, we tested whether administration of 2.5-mg·kg diazepam (i.p.) in adult male rats could block the effects of 20-mg·kg cocaine (i.p.) on electrically evoked phasic dopamine signals in the nucleus accumbens measured by fast-scan cyclic voltammetry, as well as 50-kHz USV and locomotor activity.



KEY RESULTS: Cocaine injection increased evoked dopamine signals up to threefold within 5 min, and the increase was significantly higher than baseline for at least 75 min. The injection of diazepam, 5 min after cocaine, attenuated the cocaine effect by nearly 50%, and this attenuation was maintained for at least 40 min. Behaviourally, cocaine increased the number of appetitive 50-kHz calls by about 12-fold. Diazepam significantly blocked this effect for the entire duration of the session. Also, cocaine-treated rats were more active than controls and diazepam significantly attenuated cocaine-induced locomotion, by up to 50%.



CONCLUSION AND IMPLICATIONS: These results suggest that the neurochemical and psychostimulant effects of cocaine can be mitigated by diazepam.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}