Time‐dependent exposure of nicotine and smoke modulate ultrasubcellular organelle localization of dopamine D₁ and D₂ receptors in the rat caudate‐putamen

Abstract

The correlation of the subcellular localization of dopamine D(1) and D(2) receptors (DA D(1) R, DA D(2) R) with nicotine addiction has not been studied. We demonstrated the ultrasubcellular organelle localization of DA D(1) and D(2) Rs in the caudate-putamen (CPu) area of rat brain in vivo exposed to nicotine (3 mg/day; oral) and passive cigarette smoking (500 ml each; 3 times/day) for 1, 4, and 12 weeks, respectively. Our results revealed DA D(1) R localization in the presynaptic and postsynaptic dendrites, endocytic vesicles, and secretory granules, and DA D(2) R localization in the presynaptic dendrites and vesicles. DA D(1) R immunogold particles were highly decreased in the secretory granules of CPu, and increased in the postsynaptic area and vesicles after prolonged nicotine and smoking exposures, suggesting the strong influence of long time smoking and nicotine exposures on DA D(1) R subcellular organelle localization. DA D(2) R immunoreactivity was comparatively less changed than that of the DA D(1) R. Western blot analysis also showed the differential expression of DA D(1) and D(2) R proteins upon nicotine and smoking exposures as compared to the untreated controls. Taken together, the results for the first time suggests the execution of addictive behavior of nicotine through modulation of mesolimbic dopaminergic system targeting subcellular organelle of DA D(1) and D(2) Rs in the CPu of adult rat brain that may lead to novel therapeutic approaches related to nicotine's neuropsychological disorders including drug addiction.

Involvement of Neurotransmitter and Nrf2 in Nicotine- and Cigarette Smoke-Induced Testicular Toxicity in Adult Rats

“…5 Individual organ weights, foods, and water consumption were also not varied among the different study groups (data not shown), as mentioned previously.…”

“…In the CS group, two commercially available filtered cigarette (ITC, India) were passively inhaled for 1 hour in a tightly sealed whole-body inhalation chamber, and in the nicotine group, nicotine (Nic 3-9 mg/kg BW/day; dissolved in PBS) was administered orally, for 4 and 12 weeks as per our previous protocol. 5 The doses closely mimic the amount of nicotine intake as with the CS in human; 39 hence, the animal model used here may closely resemble the human situation. The control group was given PBS.…”

“…Tissue homogenates were prepared in PBS (0.02 M, pH 7.4) followed by ultracentrifugation (12,000 rpm, 10 minutes × 2), as described previously. 5,40 Blood was collected from the hearts of the anesthetized rats through terminal bleeding procedure during euthanasia in serum separator tube (BD, USA) and, after 30 minutes, centrifuged at 1000 g for 10 minutes prior to making aliquots. 41 Samples were cryopreserved for further analysis, if required.…”

“…3,4 Nicotine has a significant influence on DAergic function of central nervous system (CNS) and modulates DAergic system targeting dopamine D1 and D2 receptors (DA D1 and D2 Rs) in the caudate putamen of the adult rat brain. 5,6 Acute doses of nicotine facilitate DA release, but chronic nicotine treatment decreases CNS DA turnover in the striatum. 7 Further, like DA, brain-derived neurotrophic factor (BDNF) is another major neurochemical that promotes cell survival, neural outgrowth, differentiation, plasticity and regeneration of damaged neurons sprouting through Trkβ R activation, and modulation of chemical synapses.…”

Neurobiological substrate of smoking-related attentional bias

“…Furthermore, Paulus et al (2005) demonstrated that activation in the insula, amongst other brain regions, predicted relapse in abstinent methamphetamine-dependent subjects. In addition, the putamen is supposed to play a role in addictive behavior through modulation of the mesolimbic dopaminergic system via D 1 and D 2 receptors (Ito et al, 2002;Naha et al, 2009). A limitation of the current study is that behavioral measures are not fully supportive for attentional bias to conditioned smoking cues in smokers.…”