Review
Biochemistry & Molecular Biology
Artem Savchenko, Giorgia Targa, Zoia Fesenko, Damiana Leo, Raul R. Gainetdinov, Ilya Sukhanov
Summary: The key element of dopamine neurotransmission is the dopamine transporter (DAT), responsible for the synaptic reuptake of dopamine. Changes in DAT function can be a mechanism of pathological conditions associated with high dopamine levels. Rodents lacking DAT exhibit increased levels of dopamine, resulting in hyperactivity, stereotypic behaviors, cognitive deficits, and other behavioral abnormalities. Pharmacological studies and the use of dopaminergic agents can alleviate these abnormalities. This review aims to analyze known data on changes in DAT expression in experimental animals, pharmacological studies in these animals, and evaluate the validity of DAT-deficient animals as models for discovering new treatments for dopamine-related disorders.
Article
Biochemistry & Molecular Biology
Marta Pardo, Michele Martin, Raul R. Gainetdinov, Deborah C. Mash, Sari Izenwasser
Summary: This study used a DAT transgenic rat model to investigate the effects of cocaine on locomotor behaviors in adolescent rats. The results showed gender differences in vulnerability to cocaine abuse in adolescence.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Cell Biology
Mei-Chuan Chou, Hsiang-Chun Lee, Yen-Chin Liu, Patrick Szu-Ying Yen, Ching-Kuan Liu, Chu-Huang Chen, Tzu-Han Hsieh, Shiou-Lan Chen
Summary: This study found that long-term consumption of a high-fat diet may cause lipid metabolism overload in the brain and damage to glial cells. This may affect the protection of the brain and the survival of specific neurons.
Article
Nutrition & Dietetics
Jian Han, Pragya Nepal, Anuoluwapo Odelade, Frederick D. Freely, Destiny M. Belton, Joseph L. Graves, Antoniette M. Maldonado-Devincci
Summary: Chronic exposure to a high-fat diet can lead to weight gain and behavioral deficits. In C57BL/6J mice, these effects begin at the 3rd month of dietary exposure and behavioral deficits occur at around 3-4 months after increased body weight.
FRONTIERS IN NUTRITION
(2021)
Article
Endocrinology & Metabolism
Sara R. Jones, Steve C. Fordahl
Summary: Binge-eating disorder disrupts dopamine neuron function by altering dopamine transporter activity. This study found that acute low-dose amphetamine can restore dopamine transporter function, but does not reduce dopamine release to normal levels caused by high-fat bingeing. This research suggests that presynaptic changes should be considered in the use of amphetamine-like dopamine releasers for treating BED.
Article
Behavioral Sciences
Giordano de Guglielmo, Attilio Iemolo, Aisha Nur, Andrew Turner, Patricia Montilla-Perez, Angelica Martinez, Caitlin Crook, Amanda Roberts, Francesca Telese
Summary: The Reelin protein encoded by the Reln gene is responsible for regulating various brain functions, including neuronal migration, dendritic growth and branching, and synapse formation. Through experiments on mice, it has been found that Reelin signaling contributes to the locomotor effects of cocaine but does not affect other behavioral responses associated with cocaine use. These findings improve our understanding of the neurobiological mechanisms underlying the effects of cocaine on cellular and behavioral levels.
GENES BRAIN AND BEHAVIOR
(2022)
Article
Biochemistry & Molecular Biology
Ilya Sukhanov, Artem Dorotenko, Zoia Fesenko, Artem Savchenko, Evgeniya V. Efimova, Mikael S. Mor, Irina V. Belozertseva, Tatyana D. Sotnikova, Raul R. Gainetdinov
Summary: Parkinson's disease is a common neurodegenerative disorder, and there is a need for new anti-parkinsonian drugs with non-dopamine mechanisms. Phosphodiesterase (PDE) 10A is a promising pharmacological target for this purpose. In this study, a rat model of acute severe dopamine deficiency was developed and validated, and the action of PDE10A inhibitor MP-10 was tested in this model. The results showed that MP-10 could effectively reverse immobility and catalepsy in rats with severe dopamine depletion, indicating its potential as a dopamine-independent therapy for Parkinson's disease.
Article
Biochemistry & Molecular Biology
Jing Deng, Ting Zhang, Xirong Zheng, Linyue Shang, Chang-Guo Zhan, Fang Zheng
Summary: Dysregulation of dopamine transporters due to cocaine exposure leads to a slow recovery process of the dopaminergic system. Acute and repeated cocaine exposures have different impacts on and recovery processes of the dopaminergic system, while a cocaine hydrolase called CocH5-Fc (M6) can effectively protect the dopaminergic system from damage caused by cocaine.
Article
Multidisciplinary Sciences
Yu Liu, Changhong Yang, Yingxue Meng, Yonghui Dang, Lin Yang
Summary: This study investigates the potential use of a ketogenic diet (KD) in treating attention deficit hyperactivity disorder (ADHD) by altering gut microbiota. The results indicate that KD can regulate gut microbiota and alleviate behavioral symptoms in ADHD. The findings provide novel insights into the use of KD as an alternative therapy for ADHD.
Article
Pharmacology & Pharmacy
Yuko Sadamura, Shanta Thapa, Ryota Mizunuma, Yuki Kambe, Akira Hirasawa, Kazuo Nakamoto, Shogo Tokuyama, Koji Yoshimoto, Kazunori Arita, Atsuro Miyata, Tatsuki Oyoshi, Takashi Kurihara
Summary: The study demonstrated that FFAR1 plays a facilitatory role in the release of 5-HT in the striatum, with the released 5-HT contributing to enhancing cocaine-induced locomotor activity.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Neurosciences
James R. Melchior, Rafael E. Perez, Gregory J. Salimando, Joseph R. Luchsinger, Aakash Basu, Danny G. Winder
Summary: This study reveals a dopamine-mediated cellular inhibition mechanism in the dBNST, suggesting that dopamine terminal autoreceptor activation and dopamine transporter blockade can affect the duration of catecholamine signals. Furthermore, cocaine enhances cellular inhibition in the dBNST in a drug reinforcement paradigm.
JOURNAL OF NEUROSCIENCE
(2021)
Article
Psychiatry
Xiuping Fu, Aparna P. Shah, Jacqueline Keighron, Ta-Chung M. Mou, Bruce Ladenheim, Jesse Alt, Daisuke Fukudome, Minae Niwa, Kellie L. Tamashiro, Gianluigi Tanda, Akira Sawa, Jean-Lud Cadet, Rana Rais, Jay M. Baraban
Summary: The study found that mice lacking the microRNA-degrading enzyme showed an exaggerated locomotor response to amphetamine and had higher brain levels of the drug, which correlated with adiposity. Diet-induced increases in adiposity also led to elevated brain levels of amphetamine in wild type mice.
TRANSLATIONAL PSYCHIATRY
(2021)
Review
Pharmacology & Pharmacy
Amy Hauck Newman, Therese Ku, Chloe J. Jordan, Alessandro Bonifazi, Zheng-Xiong Xi
Summary: Efforts to develop medications for treating psychostimulant use disorders have not been successful, with potential targets for pharmacotherapies still needing to be identified for future drug development.
ANNUAL REVIEW OF PHARMACOLOGY AND TOXICOLOGY, VOL 61, 2021
(2021)
Article
Neurosciences
Dakota B. Zinani, Hanna N. Wetzel, Andrew B. Norman
Summary: This study revealed significant differences in the intake rate, satiety threshold, and half-life of different DAT inhibitors in rats. The duration of lever-pressing following termination of drug access was correlated with the t(1/2) estimates, suggesting a relationship between the time needed for animals to stop lever pressing and the PK properties of the agonist.
Article
Biochemistry & Molecular Biology
Soheil Kazemi Roodsari, Yan Cheng, Kirstin M. Reed, Laurie L. Wellman, Larry D. Sanford, Woong-Ki Kim, Ming-Lei Guo
Summary: Sleep disorders and drug addiction are highly correlated and function as major risk factors for drug addiction. Recent studies have shown that both sleep disorders and drug abuse could activate microglia and increase neuroinflammation, which play critical roles in the pathogenesis of both diseases. Through experiments using a mouse model, it was found that sleep fragmentation (SF) can attenuate the psychoactive effects of cocaine by modulating neuroimmune and dopamine signaling. These findings suggest that sleep disorders may mediate the connection between sleep disorders and drug addiction by affecting neuroimmune and dopamine signaling in the brain reward circuitry.