• The Korean Journal of Physiology and Pharmacology
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• v.21 no.5
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• pp.487-493
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• 2017

The anterior cingulate cortex (ACC) is known for its role in perception of nociceptive signals and the associated emotional responses. Recent optogenetic studies, involving modulation of neuronal activity in the ACC, show that the ACC can modulate mechanical hyperalgesia. In the present study, we used optogenetic techniques to selectively modulate excitatory pyramidal neurons and inhibitory interneurons in the ACC in a model of chronic inflammatory pain to assess their motivational effect in the conditioned place preference (CPP) test. Selective inhibition of pyramidal neurons induced preference during the CPP test, while activation of parvalbumin (PV)-specific neurons did not. Moreover, chemogenetic inhibition of the excitatory pyramidal neurons alleviated mechanical hyperalgesia, consistent with our previous result. Our results provide evidence for the analgesic effect of inhibition of ACC excitatory pyramidal neurons and a prospective treatment for chronic pain.

• Biomolecules & Therapeutics
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• v.31 no.4
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• pp.411-416
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• 2023

Methamphetamine (METH) is a powerful neurotoxic psychostimulant affecting dopamine transporter (DAT) activity and leading to continuous excess extracellular dopamine levels. Despite recent advances in the knowledge on neurobiological mechanisms underlying METH abuse, there are few effective pharmacotherapies to prevent METH abuse leading to brain damage and neuropsychiatric deficits. α-Pinene (APN) is one of the major monoterpenes derived from pine essential oils and has diverse biological properties including anti-nociceptive, anti-anxiolytic, antioxidant, and anti-inflammatory actions. In the present study, we investigated the therapeutic potential of APN in a METH abuse mice model. METH (1 mg/kg/day, i.p.) was injected into C57BL/6 mice for four alternative days, and a conditioned place preference (CPP) test was performed. The METH-administered group exhibited increased sensitivity to place preference and significantly decreased levels of dopamine-related markers such as dopamine 2 receptor (D2R) and tyrosine hydroxylase in the striatum of the mice. Moreover, METH caused apoptotic cell death by induction of inflammation and oxidative stress. Conversely, APN treatment (3 and 10 mg/kg, i.p.) significantly reduced METH-mediated place preference and restored the levels of D2R and tyrosine hydroxylase in the striatum. APN increased the anti-apoptotic Bcl-2 to pro-apoptotic Bax ratio and decreased the expression of inflammatory protein Iba-1. METH-induced lipid peroxidation was effectively mitigated by APN by up-regulation of antioxidant enzymes such as manganese-superoxide dismutase and glutamylcysteine synthase via activation of nuclear factor-erythroid 2-related factor 2. These results suggest that APN may have protective potential and be considered as a promising therapeutic agent for METH-induced drug addiction and neuronal damage.

• Archives of Pharmacal Research
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• v.26 no.7
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• pp.540-544
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• 2003

Morphine, an analgesic with significant abuse potential, is considered addictive because of drug craving and psychological dependence. It is reported that repeated treatment of morphine can produce conditioned place preference (CPP) showing a reinforcing effect in mice. CPP is a useful method for the screening of morphine-induced psychological dependence. In the present study, we investigated the effect of the methanolic extract of Coptis japonica (MCJ) on morphine-induced CPP in mice. Furthermore, we examined c-fos expression in the parietal cortex, piriform cortex, striatum, nucleus accumbens, and hippocampus of the morphine-induced CPP mouse brain. Treatment of MCJ 100 mg/kg inhibited morphine-induced CPP. Expression of c-fos was increased in the cortex, striatum, nucleus accumbens, and hippocampus of the morphine-induced CPP mouse brain. These increases of expression were inhibited by treatment with MCJ 100 mg/kg, compared to the morphine control group. Taken together, these results suggest that MCJ inhibits morphine-induced CPP through the regulation of c-fos expression in the mouse brain.

• Biomolecules & Therapeutics
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• v.14 no.3
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• pp.125-131
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• 2006

The inhibitory effects of (-)-epigallocatechin gallate (EGCG), a major compound of green tea, on the development of locomotor sensitization, conditioned place preference (CPP) and dopamine receptor supersensitivity induced by the repeated administration of morphine were investigated in mice. A single administration of morphine produces hyperlocomotion. The repeated administration of morphine develops sensitization, a progressive enhancement of locomotion, which is used as a model for studying the craving and drug-seeking behaviors characterizing addiction, and CPP, which is used as a model for studying drug reinforcement, respectively. EGCG inhibited morphine-induced hyperlocomotion, sensitization and CPP. In addition, EGCG inhibited the development of postsynaptic dopamine receptors supersensitivity, which may be an underlying common mechanism that mediates the morphine-induced dopaminergic behaviors such as sensitization and CPP. Apomorphine (a dopamine agonist)-induced climbing behaviors also were inhibited by a single direct administration of EGCG These results provide evidence that EGCG has anti-dopaminergic activity, as inhibiting the development of dopamine receptor supersensitivity and apomorphine-induced climbing behaviors. Therefore, it is suggested that green tea may be useful for the prevention and therapy of these adverse actions of morphine.

• Archives of Pharmacal Research
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• v.29 no.10
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• pp.904-910
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• 2006

The inhibitory effects of paeonol, a major compound of Paeoniae radix, on the development of locomotor sensitization, conditioned place preference (CPP) and dopamine receptor supersensitivity induced by the repeated administration of morphine were investigated through behavioral experiments. A single administration of morphine produces hyperlocomotion. Repeated administration of morphine develops sensitization (reverse tolerance), a progressive enhancement of locomotion, which is used as a model for studying the drug-induced drug-seeking behaviors, and CPP, which is used as a model for studying drug reinforcement. Paeonol inhibited morphine-induced hyperlocomotion, sensitization and CPP. In addition, paeonol inhibited the development of postsynaptic dopamine receptors supersensitivity, which may be an underlying common mechanism that mediates the morphine-induced dopaminergic behaviors such as sensitization and CPP. Apomorphine (a dopamine agonist)-induced climbing behaviors also were inhibited by a single direct administration of paeonol. These results provide evidence that paeonol exerts anti-dopaminergic activity, and it is suggested that paeonol may be useful for the prevention and therapy of these adverse actions of morphine.

• Proceedings of the Korean Society of Applied Pharmacology
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• 1996.04a
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• pp.214-214
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• 1996

Intraperitoneal injection of morphine (5 mg/kg) in mice every other day for 8 days produced conditioned place preference (CPP). CPP effects were evaluated by assessing the difference in time spent in the drug-paired compartment and the saline-paired compartment of the place conditioning apparatus. The injection of a non-competitive NMDA antagonist, MK-801 (0.05 and 0.1 mg/kg, i.p.), prior to and during morphine treatment in mice Inhibited morphine-induced CPP. The development of postsynaptic dopamine (DA) receptor supersensitivity in mice displaying a morphine-induced CPP was evidenced by the enhanced response in ambulatory activity to the DA agonist, apomorphine (2 mg/kg). MK-801 inhibited that development of postsynaptic DA receptor supersensitivity MK-801 also inhibited apomorphine-induced climbing behavior, suggesting that MK-801 Inhibits dopaminergic activation mediated via the NMDA receptor.

• Biomolecules & Therapeutics
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• v.22 no.5
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• pp.460-466
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• 2014

Nicotine addiction is a worldwide problem. However, previous studies characterizing the rewarding and reinforcing effects of nicotine in animal models have reported inconsistent findings. It was observed that the addictive effects are variable on different factors (e.g. route, dose, and age). Here, we evaluated the rewarding and reinforcing effects of nicotine in different routes of administration, across a wide dose range, and in different age groups. Two of the most widely used animal models of drug addiction were employed: the conditioned place preference (CPP) and self-administration (SA) tests. Nicotine CPP was evaluated in different routes [intraperitoneal (i.p.) and subcutaneous (s.c.)], doses (0.05 to 1.0 mg/kg) and age [adolescent and adult rats]. Similarly, intravenous nicotine SA was assessed in different doses (0.01 to 0.06 mg/kg/infusion) and age (adolescent and adult rats). In the CPP test, s.c. nicotine produced greater response than i.p. The 0.2 mg/kg dose produced highest CPP response in adolescent, while 0.6 mg/kg in adult rats; which were also confirmed in 7 days pretreated rats. In the SA test, adolescent rats readily self-administer 0.03 mg/kg/infusion of nicotine. Doses that produced nicotine CPP and SA induced blood nicotine levels that corresponded well with human smokers. In conclusion, we have demonstrated that nicotine produces reliable CPP [0.2 mg/kg dose (s.c.)] in adolescents and [0.6 mg/kg dose (s.c.)] in adults, and SA [0.03 mg/kg/infusion] in adolescent rats. Both tests indicate that adolescent rats are more sensitive to the rewarding and reinforcing effects of nicotine.

• Biomolecules & Therapeutics
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• v.25 no.6
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• pp.659-664
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• 2017

Although lisdexamfetamine is used as a recreational drug, little research exists regarding its potential for dependence or its precise mechanisms of action. This study aims to evaluate the psychoactivity and dependence profile of lisdexamfetamine using conditioned place preference and self-administration paradigms in rodents. Additionally, biochemical techniques are used to assess alterations in the dopamine levels in striatal synaptosomes following administration of lisdexamfetamine. Lisdexamfetamine increased both conditioned place preference and self-administration. Moreover, after administration of the lisdexamfetamine, dopamine levels in the striatal synaptosomes were significantly increased. Although some modifications should be made to the analytical methods, performing high performance liquid chromatography studies on synaptosomes can aid in predicting dependence liability when studying new psychoactive substances in the future. Collectively, lisdexamfetamine has potential for dependence possible via dopaminergic pathway.

• Biomolecules & Therapeutics
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• v.20 no.2
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• pp.234-238
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• 2012

Propofol is an anesthetic commonly used to provide sedation or to induce and maintain an anesthetic stated. However, there are reports which indicate propofol may cause psychological dependence or be abused. In the present study, we used various behavioral tests including climbing test, jumping test, conditioned place preference, and self-administration test to assess the dependence potential and abuse liability of propofol compared to a positive control (methamphetamine) or a negative control (saline or intralipid). Among the tests, the conditioned place preference test was conducted with a biased method, and the selfadministration test was performed under a fixed ratio (FR) 1 schedule, 1 h per session. No difference was found in the climbing test and jumping test, but propofol (30 mg/kg, i.p.) increased the rewarding effect in the conditioned place preference test, and it showed a positive reinforcing effect compared to the vehicle. These results indicate that propofol tends to show psychological dependence rather than physical dependence, and it seems not to be related with dopaminergic system.

• Proceedings of the PSK Conference
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• 2002.04a
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• pp.119.1-119.1
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• 2002