Roles of monoamine neurotransmitters in the mechanism of drug addiction / 中国药理学通报

Drug addiction is a chronic recrudescent brain dis-ease. Various addictive drugs acting on the reward system result in rewarding effects through changes in neurotransmitter patholog-ical release. Among these monoamine neurotransmitters, 5-hydroxytryptamine, norepinephrine and dopamine play key roles in drug addiction. This paper reviews, from a comprehensive perspective, the roles which monoamine neurotransmitters play in the drug addiction and the process of getting addictive.

Efeitos da exposição à nicotina e à fumaça de cigarro durante a lactação sobre o sistema de recompensa cerebral em ratos / Effects of exposure to nicotine and cigarette smoke during lactation on the brain reward system in rats

Crianças de mães fumantes são mais suscetíveis a se tornarem adultos obesos e se viciarem em drogas ou alimentos palatáveis. Drogas e alimentos ativam a via mesolímbica de recompensa, causando sensação de prazer que induz ainda mais o consumo. Assim, avaliamos a relação entre a exposição apenas à nicotina ou à fumaça do cigarro durante a lactação com a preferência alimentar e sistema dopaminérgico de recompensa cerebral das proles, em dois modelos de programação: Modelo I: no 2o dia pós-natal (PN), lactantes receberam implante de minibombas osmóticas que liberam nicotina (NIC) ou salina (C), durante 14 dias. Em PN150 e novamente em PN160, as proles foram divididas em 4 grupos para um desafio alimentar: N-SC e C-SC que receberam ração padrão; N-SSD e C-SSD que podiam escolher livremente entre as dietas hiperlipídica e hiperglicídica. A ingestão alimentar foi avaliada após 12 h. As mães foram sacrificadas apenas na 21ª da lactação (desmame) e as proles em PN15 (com nicotina), PN21 e PN170 (ausência da NIC). Ao desmame, as ratas lactantes NIC apresentaram menor conteúdo de tirosina hidroxilase (TH), maior OBRb e SOCS3 na area tegmentar ventral (VTA); menor TH, maior receptor de dopamina 1 (D1R), receptor de dopamina 2 (D2R) e transportador de dopamina (DAT) no núcleo accumbens (NAc); maior conteúdo de TH no estriado dorsal (DS); e maior D2R e SOCS3 no núcleo arqueado (ARC). Em PN15, os filhotes NIC apresentaram maior conteúdo de D1R, D2R e menor DAT no NAc, enquanto em PN21, apresentaram apenas menor DAT no DS, e menor conteúdo de pSTAT3 em ARC. Aos 170 dias, as proles SSD demonstraram maior preferência para a ração hiperlipídica. No entanto, os animais N-SSD consumiram mais ração hiperglicidica do que as proles C-SSD...

Children from smoking mothers are more susceptible to become obese adults and to become drug or food addicts. Drugs and food activate the mesolimbic reward pathway, causing a sense of pleasure that induces further consumption.Thus, we studied the relationship between only nicotine or tobacco smoke exposure during lactation with feeding behavior and brain dopaminergic reward system at adulthood, in two programming models: Model I, on the postnatal day (PN) 2, lactating rats were implanted with minipumps releasing nicotine (NIC) or saline (C) for 14 days. On PN150 and again on PN160, offspring were divided into 4 groups for a food challenge: N-SC and C-SC received standard chow; N-SSD and C-SSD could freely select between hyperlipidic and hyperglicidic diets. Mothers were euthanized only in 21ª of lactation and offspring were euthanized in PN15 (with nicotine), PN21 and PN170 (withdraw). At weaning (PN21), NIC dams had: lower tyrosine hydroxylase (TH), higher OBRb and SOCS3 contents in ventral tegmental area (VTA); lower TH, higher dopamine receptor 1 (D1R), dopamine receptor 2 (D2R) and dopamine transporter (DAT) contents in nucleus accumbens (NAc); higher TH content in dorsal striatum (DS); and higher D2R and SOCS3 contents in arcuate nucleus (ARC). On PN15, NIC pups had higher D1R, D2R and lower DAT contents in NAc, while on PN21 they had lower DAT in DS, and lower pSTAT3 content in ARC. On PN170, SSD animals showed an increased food intake compared with SC ones and a preference for the hyperlipidic chow. However, N-SSD animals consumed relatively more hyperglicidic chow than C-SSD ones. N offspring presented lower D2R and DAT contents in the NAc, and lower D2R in the ARC. Model II, nursing rats and their pups were divided into: tobacco smoke-exposed (S group: 4 times/day, from the 3rd to the 21th day of lactation), and ambient air-exposed (C group)...

Smoking as an Addictive Disorder / 신경정신의학

Nicotine is the major substance that accounts for the addictive nature of smoking. Nicotine induces neurobiological and behavioral responses through diverse neurochemical mechanisms over the central nervous system. The brain reward system, particularly the dopaminergic pathway from the ventral tegmental area to nucleus accumbens, is central to understanding the behavioral reinforcement underlying substance addictions such as the addiction to nicotine. Nicotine acts as an agonist provoking activation or desensitization of nicotinic acetylcholine receptors in different brain areas including the brain reward system. Nicotine also indirectly influences the glutaminergic, GABAergic, noradrenergic, and serotonergic neurotransmission that lead ultimately to activation of the dopaminergic pathway in the brain reward system. Chronic exposure to nicotine activates neuroadaptation and associative learning with the nicotine-related stimulus through dopaminergic or cholinergic systems, which can lead to nicotine dependence or withdrawal. In sum, the neurobiological processes described above are deeply involved in the basis of nicotine dependence and underlie the frequent failure of attempts to quit smoking. In this review we discuss the neurobiological mechanisms of nicotine addiction focusing on the roles of the nicotinic acetylcholine receptor.

Smoking as an Addictive Disorder / 신경정신의학

Nicotine is the major substance that accounts for the addictive nature of smoking. Nicotine induces neurobiological and behavioral responses through diverse neurochemical mechanisms over the central nervous system. The brain reward system, particularly the dopaminergic pathway from the ventral tegmental area to nucleus accumbens, is central to understanding the behavioral reinforcement underlying substance addictions such as the addiction to nicotine. Nicotine acts as an agonist provoking activation or desensitization of nicotinic acetylcholine receptors in different brain areas including the brain reward system. Nicotine also indirectly influences the glutaminergic, GABAergic, noradrenergic, and serotonergic neurotransmission that lead ultimately to activation of the dopaminergic pathway in the brain reward system. Chronic exposure to nicotine activates neuroadaptation and associative learning with the nicotine-related stimulus through dopaminergic or cholinergic systems, which can lead to nicotine dependence or withdrawal. In sum, the neurobiological processes described above are deeply involved in the basis of nicotine dependence and underlie the frequent failure of attempts to quit smoking. In this review we discuss the neurobiological mechanisms of nicotine addiction focusing on the roles of the nicotinic acetylcholine receptor.