Biology subjects

Gonzalez-Segarra, A. J.

Publications and source records attributed to Gonzalez-Segarra, A. J..

3 recordsLinked to original sources

bioRxiv2024

Cocaine sensitization in male rats requires activation of estrogen receptors

Gonadal steroids play a modulatory role in cocaine use disorders, and are responsible for many sex differences observed in the behavioral response to cocaine. In females, it is well established that estradiol enhances the behavioral response to cocaine. In males, we have recently shown that testosterone enhances sensitization to cocaine but its mechanism of action remains to be elucidated. The current study investigated the contribution of DHT, a non-aromatizable androgen, and of estradiol, in regulating cocaine-induced sensitization in male rats. Gonadectomized (GDX) male rats treated with estradiol sensitized to repeated cocaine administration, while GDX rats treated with DHT did not, implicating estradiol in cocaine sensitization. Furthermore, intact male rats treated with the antiestrogen ICI 182,780 did not show sensitization to repeated cocaine. This study demonstrates the pivotal role of estradiol in cocaine-induced neuroplasticity and neuroadaptations in the rodent brain.

neuroscience↗

bioRxiv2024

Nandrolone alters the behavioral response to cocaine as well as striatal and cortical dopamine receptors of prepubertal male rats.

Nandrolone is the anabolic androgenic steroid (AAS) most used by athletes and adolescents. The use of supraphysiologic doses has been associated with dysfunction in brain areas that regulate anxiety, motivation, and reward. This study investigated if exposure to nandrolone before puberty altered anxiety- and addictive-like behaviors. Changes in dopamine type 2 receptors (D2DR) in the nucleus accumbens (NAc) and medial prefrontal cortex (mPFC) were also examined. Male rats received 10 daily injections of nandrolone decanoate (20 mg/kg) starting on day 28. Afterwards, they were tested in the elevated plus maze (EPM) and open field (OF). Their locomotor response (sensitization) and preference (conditioned place preference (CPP)) to cocaine (15 mg/kg) was also assessed. Nandrolone reduced anxiety and ambulation. Nandrolone-treated males also displayed sensitization to cocaine at an earlier age (day 44) than oil-treated males (day 52) and showed a 27% reduction in CPP to cocaine. Expression of D2DR in the NAc, and in the PFC of males tested for CPP was increased by nandrolone, whereas treatment with cocaine reduced accumbal D2DR. We hypothesize that nandrolone accelerates the development of the neural circuitry that regulates behavioral sensitization and reduces the rewarding property of cocaine, as manifested in the reduction of CPP. It is possible that the observed increase in accumbal D2DR may partially mediate the reduced anxiety and ambulation as well accelerate the maturation of the neural circuitry responsible for the sensitized response to cocaine.

neuroscience↗

bioRxiv2023

Hunger- and thirst-sensing neurons modulate a neuroendocrine network to coordinate sugar and water ingestion

Consumption of food and water is tightly regulated by the nervous system to maintain internal nutrient homeostasis. Although generally considered independently, interactions between hunger and thirst drives are important to coordinate competing needs. In Drosophila, four neurons called the Interoceptive Subesophageal zone Neurons (ISNs) respond to intrinsic hunger and thirst signals to oppositely regulate sucrose and water ingestion. Here, we investigate the neural circuit downstream of the ISNs to examine how ingestion is regulated based on internal needs. Utilizing the recently available fly brain connectome, we find that the ISNs synapse with a novel cell type Bilateral T-shaped neuron (BiT) that projects to neuroendocrine centers. In vivo neural manipulations revealed that BiT oppositely regulates sugar and water ingestion. Neuroendocrine cells downstream of ISNs include several peptide-releasing and peptide-sensing neurons, including insulin producing cells (IPC), crustacean cardioactive peptide (CCAP) neurons, and CCHamide-2 receptor isoform RA (CCHa2R-RA) neurons. These neurons contribute differentially to ingestion of sugar and water, with IPCs and CCAP neurons oppositely regulating sugar and water ingestion, and CCHa2R-RA neurons modulating only water ingestion. Thus, the decision to consume sugar or water occurs via regulation of a broad peptidergic network that integrates internal signals of nutritional state to generate nutrient-specific ingestion.

neuroscience↗