Progress in Neuro-Psychopharmacology and Biological Psychiatry
Dopamine D1 and D2 receptor mRNA up-regulation in the caudate–putamen and nucleus accumbens of rat brains by smoking
Introduction
Nicotine can produce a wide array of behavioral abnormalities, some of which collectively propel drug-seeking behavior (Shoaib, 1998) just like other addictive drugs when abused. Already, many behavioral effects of nicotine in animals and man are widely understood. That smoking is a powerful addictive drug has been already summarized in the US Surgeon General's Report in 1988 (United States Dept. Health, 1988), and strengthened by further research showing similarities between nicotine and a number of addictive drugs including cocaine, amphetamine and heroin. The major source of nicotine in human is tobacco smoking and nicotine is the primary component that drives addiction (Pidoplichko et al., 1997). Nicotine is regarded as a toxic substance absorbed by smoking and it is clear that smoking is harmful for brain Dani and Heinemann, 1996, Iversen, 1996, Shoaib, 1998.
Dopamine (DA) is an important neurotransmitter that has reward and reinforcing properties just like many addictive drugs (Di Chiara and Imperato, 1988). DA is a mediator that controls many aspects of cognitive, emotional, motor and endocrine function Wickens, 1990, Glenthoj, 1995, Gerfen and Wilson, 1996. The pathologic condition of DA systems is implicated in a number of disorders, including schizophrenia, mood disorder, drug addition and attention deficit hyperactivity disorder Koob, 1992, Brown and Gershon, 1993, Hunt et al., 1994, Self and Nestler, 1995, Searight et al., 1995, Knable et al., 1997, Sagvolden and Sergeant, 1998, Fang and Rønnekleiv, 1999. In epidemiological studies, tobacco smoking has been associated with Parkinson's disease and Alzheimer's disease Strange, 1993, Lee, 1994, Morens et al., 1995, Baron, 1996, Dalack et al., 1998. Levels of DA in the mesostriatal and mesocorticolimbic circuits, and DA receptors in other regions of the brain are likely to be modulated by tobacco smoking.
DA acts on the DA receptor subtypes of several areas in brain. DA receptors can be divided into five subtypes that cluster into two families, D1 and D5 and D2 to D4 Monsma et al., 1990, Bunzow et al., 1998. These receptors are found in the caudate–putamen (CPu), olfactory tubercle (OTu), nucleus accumbens (NAc), cortex and hippocampus of the brain Angulo et al., 1991, Fremeau et al., 1991.
The most important DA pathway originates in the ventral tegmental area of the midbrain and projects to forebrain structures including the prefrontal cortex and to limbic areas such as the CPu, amygdala, septal region and the NAc. The NAc, a small DA-rich brain region situated ventrally at the head of the CPu, plays a crucial role in the rewarding effects of these addictive drugs Koob, 1992, Pontieri et al., 1996. In spite of many previous studies that have focused on the regulation of striatal DA receptors by nicotine treatment, not much is known about the regulation of DA receptors by smoking. The effect of smoking itself on the expression of DA receptors, therefore, has to be elucidated.
The aim of this study is to compare the influence of smoking and nicotine addiction on the regulation of DA D1 and D2 receptor mRNA expression in the CPu, OTu and NAc area of rat brain.
Section snippets
Animals and grouping
Male (n=50) Spraque–Dawley rats (250 g, Gyeongsang National University, Animal Breeding Center, Jinju, Korea) were housed in a temperature-controlled environment under lights from 06:00 to 20:00 h with food ad libitum. The rats were divided into two, 10 in the control group and 40 in the experimental group. The experimental groups were further divided into two groups: the smoking group and the nicotine group. In the smoking group, cigarette smoke was passive inhaled by inhalant for 10 min for
Change of DA D1 receptor mRNAs
DA D1 receptor mRNA signals were detected in the CPu, NAc and OTu by in situ hybridization Fig. 1, Fig. 2, Fig. 3. However, the sense probe failed to show any signals (data not shown). Smoke (10 min and 1 h) up-regulated DA D1 receptor mRNA highly in all examined areas Fig. 1, Fig. 2, Fig. 3 and increased density of silver grains. Quantitative analysis of the DA D1 receptor mRNAs in the 10 min group showed increased densities (+105.4% for CPu, +82.6% for NAc and +10.4% for OTu) than in the
Discussion
The close relation between nicotine and smoking is widely understood among the general populace. Addiction to smoking is attributed to nicotine with the major component in cigarette (Dalack et al., 1998). Smoking has many harmful effects including cancer, and for these reasons, the increased number of young smokers in young people must be considered as a serious social problem. A recent report from Iversen (1996) revealed that both DA D1 and D2 receptors are important in smoking and nicotine
Conclusions
Smoking and nicotine up-regulate the expression of DA D1 and D2 receptor mRNAs in the CPu and NAc of rat brains. Although the role of nicotine in up-regulation is evident, smoking tends not only to up-regulate DA receptor mRNA expression more than the nicotine but also to up-regulate more the CPu and NAc than the OTu.
Acknowledgements
This work was supported by Korea Research Foundation Grant (KRF-2000-015-DP0405).
References (39)
- et al.
Demonstration of tissue specific gene expression by in situ hybridization
Methods Endocrinol.
(1987) - et al.
Regulation by dopaminergic neurotransmission of dopamine D2 mRNA and receptor level in the striatum and nucleus accumbens of the rat
Mol. Brain Res.
(1991) - et al.
Chronic prenatal cocaine treatment down-regulates μ-opioid receptor mRNA expression in the brain of fetal Rhesus macaque
Neurosci. Lett.
(1999) - et al.
Molecular and cellular aspects of nicotine abuse
Neuron
(1996) Role of dopamine in the behavioural actions of nicotine related to addiction
Eur. J. Pharmacol.
(2000)- et al.
The basal ganglia
Drugs of abuse: anatomy, pharmacology and function of reward pathways
Trends Pharmacol. Sci.
(1992)- et al.
A single (−)-nicotine injection causes change with a time delay in the affinity of striatal D2 receptors for antagonist, but not for agonist, nor in the D2 receptor mRNA levels in the rat substantia nigra
Brain Res.
(1995) Is dopamine important in nicotine dependence?
J. Physiol.
(1998)Beneficial effects of nicotine and cigarette smoking: the real the possible and the spurious
Br. Med. Bull.
(1996)
Dopamine and depression
J. Neural Transm.
Cloning and expression of a rat dopamine D2 receptor cDNA
Nature
The effects of dopaminergic D2 stimulation and blockade on smoking behavior
Exp. Clin. Psychopharmacol.
Maternal cocaine treatment alters dynorphin and enkephalin mRNA expression in brains of fetal rhesus macaques
J. Neurosci.
Nicotine dependence in schizophrenia: clinical phenomena and laboratory findings
Am. J. Psychiatry
p1B15: a cDNA clone of the rat mRNA encoding. Cyclophilin
DNA
Drugs abused by humans preferentially increase synaptic dopamine concentrations in the mesolimbic system of freely moving rats
Proc. Natl. Acad. Sci.
Cocaine upregulates the dopamine transporter in fetal rhesus monkey brain
J. Neurosci.
Localization of D1 dopamine receptor mRNA in brain supports a role in cognitive, affective, and neuroendocrine aspects of dopaminergic neurotransmission
Proc. Natl. Acad. Sci.
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