Biology subjects

Ding, Z.-M.

Publications and source records attributed to Ding, Z.-M..

3 recordsLinked to original sources

bioRxiv2026

Ethanol drinking involves astrocytes in male Wistar rats

Astrocytes are the most abundant glial cells in the brain and an integrative component of the neural network. Studies have shown that ethanol altered expression of an astrocyte marker, i.e., glial fibrillary acidic protein (GFAP), in two key corticolimbic regions, the medial prefrontal cortex (mPFC) and nucleus accumbens (NAc). These regions comprise anatomically and functionally different subregions, i.e., the prelimbic (PL) and infralimbic (IL) cortex of the mPFC, the shell and core subregions of the NAc. However, ethanol effects on GFAP expression within these subregions remain largely unknown. In addition, effects of pharmacological manipulation of astrocytes on alcohol drinking have been understudied. Western blot was conducted to determine GFAP expression in subregions of the mPFC and NAc after chronic ethanol drinking. Fluorocitrate, an astrocyte-specific metabolic inhibitor, was administered to inhibit astrocytes and was tested on ethanol drinking. Ethanol drinking enhanced GFAP protein expression in the PL cortex and NAc core, but not in the IL cortex or NAc shell. Intra-ventricular administration of fluorocitrate reduced ethanol intake and preference, but increased water consumption during choice ethanol drinking. In addition, fluorocitrate did not affect total fluid consumption or basal locomotor activity. These results indicate that chronic ethanol drinking induced GFAP elevation in a subregion-specific manner within the mPFC and NAc, and that metabolic inhibition of astrocytes selectively attenuated ethanol drinking without non-specific effects on water drinking or general activity. Together, these results suggest that astrocytes may play an important role in ethanol drinking. HighlightsO_LIEthanol drinking enhanced GFAP levels in the PL cortex and NAc core. C_LIO_LIFluorocitrate inhibition of astrocytes reduced intermittent ethanol drinking. C_LIO_LIFluorocitrate did not alter total fluid consumption or basal locomotor activity. C_LI

neuroscience↗

bioRxiv2023

Methoxsalen inhibited the acquisition of nicotine self-administration: attenuation by cotinine replacement in rats

Cigarette smoking remains the leading preventable cause of disease and death. Nicotine is the primary reinforcing ingredient in cigarettes sustaining addiction. Cotinine is the major metabolite of nicotine that produces a myriad of neurobehavioral effects. Cotinine supported self-administration and rats with a history of intravenous self-administration of cotinine exhibited relapse-like drug-seeking behavior, suggesting cotinine may also be reinforcing. To date, a potential contribution of cotinine to nicotine reinforcement remains unknown. Nicotine metabolism is mainly catalyzed by hepatic CYP2B1 enzyme in the rat and methoxsalen is a potent CYP2B1 inhibitor. The study tested the hypothesis that methoxsalen inbibits nicotine metabolism and self-administration, and that cotinine replacement attenuates the inhibitory effects of methoxsalen. Acute methoxsalen decreased plasma cotinine levels and increased nicotine levels following subcutaneous nicotine injection. Repeated methoxsalen reduced the acquisition of nicotine self-administration, leading to fewer nicotine infusions, disruption of lever differentiation, smaller total nicotine intake, and lower plasma cotinine levels. On the other hand, methoxsalen did not alter nicotine self-administration during the maintenance phase despite great reduction of plasma cotinine levels. Cotinine replacement by mixing cotinine with nicotine for self-administration dose-dependently increased plasma cotinine levels, counteracted effects of methoxsalen, and enhanced the acquisition of self-administration. Neither basal nor nicotine-induced locomotor activity was altered by methoxsalen. These results indicate that methoxsalen depressed cotinine formation from nicotine and the acquisition of nicotine self-administration, and that replacement of plasma cotinine attenuated the inhibitory effects of methoxsalen, suggesting that cotinine may contribute to the development of nicotine reinforcement.

neuroscience↗

bioRxiv2021

Relapse to cotinine seeking in rats: Differential effects of sex

Relapse is a defining feature of smoking and a significant challenge in cessation management. Elucidation of novel mechanisms underlying relapse may inform future treatments. Cotinine, the major metabolite of nicotine, has been shown to support intravenous self-administration in rats, suggesting it as one potential mechanism contributing to nicotine reinforcement. However, it remains unknown whether cotinine would induce relapse-like behaviors. The current study investigated relapse to cotinine seeking in two relapse models, the reinstatement of drug seeking and incubation of drug craving models. In the reinstatement model, rats were trained to self-administer cotinine, extinguished cotinine-associated responses, and underwent cue-, drug-, or stress-induced reinstatement. Conditioned cues associated with cotinine self-administration, cotinine (1-2 mg/kg), or the pharmacological stressor yohimbine (1.25-2.5 mg/kg) reinstated cotinine seeking. Female rats displayed more pronounced cue-induced, but not drug- or stress-induced reinstatement than male rats. In addition, an overall analysis revealed that female rats exhibited greater cotinine self-administration, but less extinction than male rats. In the incubation model, rats were trained to self-administer cotinine, and underwent forced withdrawal in home cages. Rats were tested for cue-induced cotinine seeking on both withdrawal day 1 and withdrawal day 18. Rats exhibited greater cotinine-seeking on withdrawal day 18 compared to withdrawal day 1, with no difference between male and female rats. These findings indicate that cotinine induces sex-dependent relapse to cotinine seeking in rats, suggesting that cotinine may be a novel mechanism contributing to relapse. These rat models are valuable preclinical tools for interrogation of neurobiological underpinnings of relapse to cotinine seeking. Significance StatementRelapse is a defining feature of smoking and a significant challenge in cessation management. Elucidation of novel mechanisms underlying relapse may inform future treatment. Cotinine, the major metabolite of nicotine, has previously been shown as a potential mechanism underlying the development of nicotine reinforcement because it supports intravenous self-administration in rats. The current study found that conditioned cues, priming injection of cotinine, and acute exposure to the pharmacological stressor yohimbine induced robust cotinine-seeking behavior in rats with a history of cotinine self-administration. In addition, significant sex effects were revealed in that female rats exhibited greater cotinine self-administration, less extinction, and more robust cue-induced reinstatement of cotinine seeking than male rats. These findings suggest that cotinine may be a novel mechanism contributing to relapse to nicotine seeking. In addition, these rat models are valuable preclinical tools for interrogation of behavioral and neurobiological underpinnings to relapse to cotinine seeking, thus forming basis for developing effective therapeutic strategy to aid in smoking cessation.

animal behavior and cognition↗