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1.
Chinese Pharmacological Bulletin ; (12): 1623-1627, 2023.
Article in Chinese | WPRIM | ID: wpr-1013717

ABSTRACT

Drug discrimination is a behavioral pharmacological technique to study the discriminative stimulus effects of drug. Currently drug discrimination has been widely used in preclinical drug development of CNS drugs, the most extensive of which is psychodependent research in the field of drug abuse. This review describes in general the basic principles of drug discrimination, preliminarily elaborates on the relevant characteristics and applications of the subjective effects, time-course effect, stereo specificity, individual differences, and receptor mechanisms, and its development prospects for hallucinogens and cannabis drugs are also presented.

2.
Article in Chinese | WPRIM | ID: wpr-1009835

ABSTRACT

Since December 2019, coronavirus disease 2019 (COVID-19) has been rapidly spreading worldwide and affecting the physical and mental health of the general population. It may have even more serious potential harm to children with autism spectrum disorder (ASD). This paper provides a literature review on the psychological and behavioral problems experienced by children with ASD during the COVID-19 epidemic, as well as the factors influencing these issues. The findings of this review can serve as a basis for clinical research on ASD children.


Subject(s)
Humans , Child , Problem Behavior , COVID-19 , Autism Spectrum Disorder , Epidemics
3.
Article in Chinese | WPRIM | ID: wpr-1015857

ABSTRACT

Substance addiction is considered to be a chronic recurrent encephalopathy. The neural adap-tation changes induced by addictive substances are partly mediated by epigenetic mechanism. The perma ̄nent changes of gene expression in tissues or brain can be affected by DNA methylation, histone modifica-tion and chromatin remodeling, these changes eventually lead to behavioral abnormalities of individual. Methyl-CpG binding protein 2 (MeCP2), an important transcription inhibitor, contains characteristic do-mains that regulated chromosome conformation, transcription and RNA splicing. It has also been identified that MeCP2 plays an important role in regulating neuronal plasticity and related target gene transcription during brain development, which add more attention about the importance of epigenetic mechanism in neuronal function. Studies have showed that DNA methylation, histone acetylation and phosphorylation regulate MeCP2 gene expression, affect gene and protein transcription, translation and cell regulation in learning, memory and substance addiction. Addictive substances induce psychological and mental dependence, which are related to the changes of neuronal plasticity and gene expression in addictive neural circuits. MeCP2 plays an important role in regulating synaptic transmission and neuronal plasticity in central nervous system. Therefore, it is of great scientific significance to explore the role of MeCP2 in regulating neuronal plasticity in the central nervous system. In this review we summarized the structure and function of MeCP2, the relationship between MeCP2 and epigenetics, and the role of MeCP2 epigenetic modifications induced by different addictive substances in substance addiction, which may provide further understanding of the molecular mechanism of substance addiction and provide new in ̄sight for clinical intervention.

4.
Article in Chinese | WPRIM | ID: wpr-814080

ABSTRACT

OBJECTIVE@#To explore the effect of electroacupuncture on heroin seeking behavior and FosB expression in relevant brain regions.@*METHODS@#Rat model of heroin relapse behaviors was developed with progressive fixed ratio program,and model rats were randomly divided into 3 groups: a restraint group, a needle retention group, and a electroacupuncture group. The heroin seeking behavior was elicited by a small dose of heroin. FosB expression in relevnt brain region was assessed with immunohistochemical technique.@*RESULTS@#Tests on reinstatement of drug seeking behavior induced by heroin priming showed that compared with the restraint group, active pokes in the electroacupuncture group decreased significantly(P<0.05). Compared with the restraint group, the expression of FosB positive nuclei in Acd, Pcg and CeA of rats brain both in the electroacupuncture group and the needle retention group (P<0.05) decreased significantly. In LC, the expression of FosB positive nuclei in the needle retention group decreased significantly compared with the restraint group (P<0.05).@*CONCLUSION@#Continuous acupuncture and needle retention attentuate the reinstatement of heroin-seeking behaviors induced by heroin priming, and the inhibitory effect may be mediated partially by the expression of FosB in relevant regions which are involved in the process of heroin addiction.


Subject(s)
Animals , Male , Rats , Amygdala , Metabolism , Behavior, Animal , Brain , Metabolism , Electroacupuncture , Methods , Heroin Dependence , Metabolism , Psychology , Therapeutics , Nucleus Accumbens , Metabolism , Proto-Oncogene Proteins c-fos , Random Allocation , Rats, Sprague-Dawley
5.
Article in Chinese | WPRIM | ID: wpr-297003

ABSTRACT

<p><b>OBJECTIVE</b>To compare effects of catgut embedding at "Zusanli" (ST 36) and "Shenshu" (BL 23) on Morphine analgesic tolerance and locomotor sensitization induced by chronic Morphine administration and the mechanism.</p><p><b>METHODS</b>The rats were randomly divided into a model group, a non-acupoint group, a Shenshu group and a Zusanli group. The rats, except those in the model group, were pretreated with acupoint catgut-embedding 10 days before the first Morphine injection. The Morphine-tolerance model was established and the pain threshold was detected by hot-plate test every day. Locomotor activities were recorded after the first Morphine injection and Morphine-challenging 1 week after withdrawal of Morphine. The positive neurons of nitric oxide synthetase (NOS) were showed by NADPH-d histochemical method.</p><p><b>RESULTS</b>Compared with the non-acupoint group, catgut embedding at "Zusanli" (ST 36) could attenuate the Morphine analgesic tolerance and the increase of locomotor activities in rats. Meanwhile, the expression of NOS positive neurons in nucleus accumbens septi and dorsal striatum decreased in the Zusanli group. There were no significant differences between the Shenshu group and the non-acupoint group in the analgesic threshold and locomotor sensitization, but the expression of NOS positive neurons in the striatum region significantly decreased.</p><p><b>CONCLUSION</b>Catgut embedding at "Zusanli" (ST 36) can attenuate Morphine analgesic tolerance and reverse formation of locomotion sensitization induced by chronic Morphine administration, which are possibly related with inhibition of the expression of NOS positive neurons in nucleus accumbens septi and dorsal striatum.</p>


Subject(s)
Animals , Male , Rats , Acupuncture Analgesia , Acupuncture Points , Analgesics, Opioid , Pharmacology , Catgut , Drug Tolerance , Medicine, Chinese Traditional , Morphine , Pharmacology , Motor Activity , Rats, Sprague-Dawley
6.
Neuroscience Bulletin ; (6): 1-8, 2007.
Article in English | WPRIM | ID: wpr-301005

ABSTRACT

<p><b>OBJECTIVE</b>To investigate the effect of M(5) muscarinic receptor subtype on the locomotor sensitization induced by heroin priming, and it's effect on the FosB expression in the nucleus accumbens (NAc) and the hippocampus in the heroin sensitized rats.</p><p><b>METHODS</b>Locomotor activity was measured every 10 min for 1 h after subcutaneous injection of heroin. FosB expression was assayed by immunohistochemistry, and the antisense oligonucleotides (AS-ONs) targeting M(5) muscarinic receptor was transferred with the lipofectin.</p><p><b>RESULTS</b>Microinjection of AS-ONs targeting M(5) muscarinic receptor in the ventral tegmental area (VTA) blocked the expression of behavioral sensitization induced by heroin priming in rats. Meanwhile, the expression of FosB-positive neurons in either the NAc or the dentate gyrus (DG) of the hippocampus increased in heroin-induced locomotor sensitized rats. The enhancement of FosB-positive neurons in the NAc or DG could be inhibited by microinjection of M(5) muscarinic receptor AS-ONs into the VTA before the heroin-induced locomotor sensitization was performed. In contrast, microinjection of M(5) muscarinic receptor sense oligonucleotide (S-ONs) into the VTA did not block the expression of behavioral sensitization or the expression of FosB in the NAc or DG in the heroin sensitized rats.</p><p><b>CONCLUSION</b>Blocking M(5) muscarinic receptor in the VTA inhibits the expression of heroin-induced locomotor sensitization, which is associated with the regulation of FosB expression in the NAc and hippocampus neurons. M(5) muscarinic receptor may be a useful pharmacological target for the treatment of heroin addiction.</p>


Subject(s)
Animals , Male , Rats , Acetylcholine , Metabolism , Brain , Metabolism , Heroin , Heroin Dependence , Drug Therapy , Metabolism , Hippocampus , Metabolism , Immunohistochemistry , Microinjections , Motor Activity , Physiology , Narcotics , Neural Pathways , Metabolism , Neurons , Metabolism , Nucleus Accumbens , Metabolism , Oligonucleotides, Antisense , Pharmacology , Proto-Oncogene Proteins c-fos , Metabolism , Rats, Sprague-Dawley , Receptor, Muscarinic M5 , Genetics , Metabolism , Synaptic Transmission , Physiology , Ventral Tegmental Area , Metabolism
7.
Article in Chinese | WPRIM | ID: wpr-348427

ABSTRACT

<p><b>OBJECTIVE</b>To observe effects of electroacupuncture (EA) of low frequency on heroin-seeking behavior and FosB protein expression in relative brain regions so as to explore the mechanism of EA.</p><p><b>METHODS</b>Rat model of relapsing into heroin was established with progressive fixed ratio program, and model rats were randomly divided into 3 groups: a "Sanyinjiao" needle-retention control group, a low frequency and weak EA group, and a low frequency and strong EA group. Heroin-seeking behavior was elicited by conditional clue and small dose of heroin; FosB protein expression was investigated with immunohistochemical technique.</p><p><b>RESULTS</b>After treatment, the heroin-seeking behavior induced by conditional clue decreased in the needle-retention control group and the weak EA group, and the heroin-seeking behavior induced by small dose of heroin in the weak EA group significantly reduced as compared with the control group, and FosB protein expression in the nucleus accumbens septi, globus pallidus, basolateral amygdaloid nucleus significantly decreased in the weak EA group, and did not significantly change in the strong EA group; the activity induced by heroin increased as compared with those in the control group and the weak EA group.</p><p><b>CONCLUSION</b>EA of low frequency and low intensity can cure the heroin-seeking behavior, which is correlated with regulating nervous adaptation of nucleus accumbens septi, basolateral amygdaloid nucleus, etc..</p>


Subject(s)
Animals , Male , Rats , Amygdala , Chemistry , Electroacupuncture , Methods , Globus Pallidus , Chemistry , Heroin Dependence , Therapeutics , Immunohistochemistry , Nucleus Accumbens , Chemistry , Proto-Oncogene Proteins c-fos , Rats, Sprague-Dawley
8.
Acta Physiologica Sinica ; (6): 95-100, 2004.
Article in Chinese | WPRIM | ID: wpr-290882

ABSTRACT

The antisense approach and RT-PCR were used to study the effects of muscarinic receptors on the scores of morphine-withdrawal syndrome and the expression of NMDA receptor subtypes (NR(1A) and NR(2A)) mRNA in rat spinal cord and brainstem. The concentrations of glutamate in periaqueductal grey (PAG) of morphine-withdrawal rats were determined by capillary electrophoresis with laser-induced fluorescence detection. The data showed that the NR(1A) and NR(2A) mRNA levels were increased significantly in the spinal cord and brainstem 1 h after the injection of naloxone (4 mg/kg, i.p.) in morphine-dependent rats. Moreover, in morphine-dependent rats pretreated (i.p.) with scopolamine (0.5 mg/kg), or pirenzepine (10 mg/kg), MK801 (0.125 mg/kg), L-N-nitroarginine methylester (10 mg/kg) 30 min before naloxone injection, the NR(1A) and NR(2A) mRNA levels were significantly lower than those of 1 h morphine-withdrawal rats. Intrathecal injection of NR(1A) or M(2) receptor antisense oligonucleotides (A-oligo, 4 microg/per rat) 24 h prior to naloxone challenge could block the morphine withdrawal symptoms including wet dog shaking, irritability, salivation, diarrhea, chewing and weight loss. Meanwhile, in morphine-dependent rats the NR(1A) mRNA levels in the spinal cord and brainstem were down-regulated by intrathecal injection of M(2) receptor A-oligo. The glutamate concentrations in PAG microdialysis were increased to a maximal level 15 min after naloxone injection. The glutamate response was inhibited by pretreatment with M(2) receptor A-oligo but not by M(1) A-oligo. The results suggest that the expression of NMDA receptors and the release of glutamate in brainstem are involved in the processes of morphine withdrawal and that the NMDA receptor expression is possibly regulated by the muscarinic receptors during morphine withdrawal.


Subject(s)
Animals , Male , Rats , Brain Stem , Metabolism , Glutamic Acid , Metabolism , Morphine , Periaqueductal Gray , Metabolism , Physiology , Rats, Sprague-Dawley , Receptors, Muscarinic , Physiology , Receptors, N-Methyl-D-Aspartate , Genetics , Spinal Cord , Metabolism , Substance Withdrawal Syndrome , Genetics , Metabolism
9.
Acta Pharmaceutica Sinica ; (12): 611-615, 2002.
Article in Chinese | WPRIM | ID: wpr-312070

ABSTRACT

<p><b>AIM</b>To observe mRNA expression of muscarinic acetylcholine receptors in spinal cord and brainstem in morphine dependent or withdrawal rats.</p><p><b>METHODS</b>The mRNA expression level of m1, m2, m3, m4 and m5 were determined by RT-PCR, the beta-actin mRNA expression was used as internal control.</p><p><b>RESULTS</b>The mRNA level of m1, m2, m3, m4 and m5 in spinal cord and m1 and m2 in brainstem were increased significantly during morphine dependence, and the levels of m1, m2, m3 and m4 in spinal cord and m1 in brainstem were decreased 1 h after the injection of naloxone (4 mg.kg-1, i.p.) in morphine dependent rats. Either scopolamine (0.5 mg.kg-1) or pirenzepine (10 mg.kg-1) was shown to significantly decrease the morphine withdrawal symptoms in rats. The levels of m1, m2, m3 and m5 in spinal cord were increased by pretreatment with pirenzepine and the levels of m2, m3 and m4 in spinal cord were increased by pretreatment with scopolamine.</p><p><b>CONCLUSION</b>The adaptive expression of muscarinic receptors at spinal and supraspinal levels play important role in mediating morphine dependence and withdrawal in rats.</p>


Subject(s)
Animals , Male , Rats , Brain Stem , Metabolism , Gene Expression , Morphine , Toxicity , Morphine Dependence , Metabolism , RNA, Messenger , Rats, Sprague-Dawley , Receptors, Muscarinic , Classification , Genetics , Spinal Cord , Metabolism , Substance Withdrawal Syndrome , Metabolism
10.
Article in Chinese | WPRIM | ID: wpr-677132

ABSTRACT

Aim To observe the gene expression of ? and ? opiate receptor in spinal cord and brainstem,and the effects of muscarinic receptor antagonist, NMDA receptor antagonists and inhibitor of nitric oxide synthase on the expression of these genes during morphine withdrawal in rats. Methods The mRNA levels of ? and ? opiate receptor mRNA were assayed by reverse transcription polymerase chain reaction (RT_PCR) with the beta_actin mRNA as an internal control. Results The ? opiate receptor mRNA levels were increased significantly in spinal cord and brainstem during morphine dependence, and decreased after injection of naloxone during morphine withdrawal in rats. The ? opiate receptor mRNA levels in spinal cord and brainstem were changed conversely compared with the ? opiate receptor mRNA levels during morphine dependence and withdrawal. The ? and ? opiate receptor mRNA levels in spinal cord and brainstem were decreased by administration of either Rp_cAMPs or calyculin A while these levels were not changed by Sp_cAMPs at half hour before injection of naloxone in morphine dependent rats. Administration of l_N_nitric arginine methylester(10 mg?kg-1) resulted in a decrease of ? opiate receptor and ? opiate receptor levels in spinal cord , and ? opiate receptor levels in spinal cord and ? opiate receptor levels in brainstem were dedcreased by pretreatment with methyl_scopolamine (0.5 mg?kg-1) during morphine withdrawal. However, the ? and ? opiate receptor levels in both spinal cord and brainstem were not different from those of morphine withdrawal rats pretreated with either MK801 (0.125 mg?kg-1) or pirezenpine(10 mg?kg-1). In adddition, ?_actin mRNA levels were not different in each group.Conclusion The expression of ? opiate receptor and ? opiate receptor mRNA plays an important role in mediating the process of morphine dependence and withdrawal, and the expression of ? opiate receptor and ? opiate receptor mRNA in spinal cord and brainstem could be inhibited by block of muscarinic receptor or inhibition of nitric oxide production.

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