Dopamine D1 and D2 receptor mRNA up-regulation in the caudate–putamen and nucleus accumbens of rat brains by smoking

doi:10.1016/S0278-5846(02)00243-9

Progress in Neuro-Psychopharmacology and Biological Psychiatry

Volume 26, Issue 6, October 2002, Pages 1095-1104

https://doi.org/10.1016/S0278-5846(02)00243-9 Get rights and content

Abstract

Nicotine, the toxic substance that is exclusively absorbed from smoking, produces a wide array of behavior and collectively propels drug-seeking behaviors when abused. The neurotransmitter dopamine (DA) is important in the reward and reinforcing properties of many addictive drugs: however, the effect of nicotine by cigarette smoking itself on the expression of DA receptors in the caudate–putamen (CPu), nucleus accumbens (NAc) and olfactory tubercle (OTu) has not been elucidated completely. Hence, the effects of smoking and nicotine on DA receptors need to be defined. In this research, the effect of smoking and nicotine addiction on the DA D₁ and D₂ receptors in the rat CPu, NAc and OTu were studied. Adult male Spraque–Dawley (S.D., n=50) rats were administered with cigarette smoke (passive inhaled for 10 min and 1 h, 500 ml×3 times/day, 4 weeks) and nicotine (oral, 3 mg/day). DA D₁ and D₂ receptor mRNA levels were determined by in situ hybridization and RNase protection assay (RPA). In the smoking groups (10 min and 1 h), DA D₁ and D₂ receptor mRNA greatly increased in the CPu and NAc, and most of all in the NAc. The nicotine treated group showed increased expression of DA D₁ and D₂ receptor mRNA too, but statistically less than in the smoking group. In the smoking group, DA D₁ and D₂ receptor mRNA levels were significantly higher in the CPu and NAc than in the nicotine group (P<.01). These results suggest that smoking and nicotine administration both influence DA receptor mRNAs in the CPu, NAc and OTu, in terms of up-regulation. The up-regulation was much more evident in the smoking group than in the nicotine group. In conclusion, we believe that smoking up-regulate the DA receptor mRNA expression significantly higher in rat CPu and NAc than nicotine but only a little bit higher in OTu.

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).

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Dopamine D1 and D2 receptor mRNA up-regulation in the caudate–putamen and nucleus accumbens of rat brains by smoking

Abstract

Introduction

Section snippets

Animals and grouping

Change of DA D1 receptor mRNAs

Discussion

Conclusions

Acknowledgements

Methods Endocrinol.

Mol. Brain Res.

Neurosci. Lett.

Neuron

Eur. J. Pharmacol.

Trends Pharmacol. Sci.

Brain Res.

J. Physiol.

Beneficial effects of nicotine and cigarette smoking: the real the possible and the spurious

Br. Med. Bull.

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.

Dopamine D₁ and D₂ receptor mRNA up-regulation in the caudate–putamen and nucleus accumbens of rat brains by smoking

Change of DA D₁ receptor mRNAs

Cloning and expression of a rat dopamine D₂ receptor cDNA

The effects of dopaminergic D₂ stimulation and blockade on smoking behavior

Localization of D₁ dopamine receptor mRNA in brain supports a role in cognitive, affective, and neuroendocrine aspects of dopaminergic neurotransmission