ABSTRACT
Substance-related and addictive disorders (SRADs) are characterized by compulsive drug use and recurrent relapse. The persistence of pathological drug-related memories indisputably contributes to a high propensity to relapse. Hence, strategies to disrupt reconsolidation of drug reward memory are currently being pursued as potential anti-relapse interventions. Sulfur dioxide (SO2), acting as a potential gaseous molecule, endogenously derives from sulfur amino acid and can exert significant neural regulatory effects. However, the role of SO2 in reconsolidation of drug memory has not been determined. In the present study, we used morphine- or cocaine-induced conditioned place preference (CPP) mouse models with retrieval to investigate the effects of exogenous SO2 donor treatment on reconsolidation of drug reward memory. We found that administration of SO2 donor immediately after the retrieval impaired the expression of morphine or cocaine CPP. Furthermore, the exogenous SO2 donor treatment 6 h post-retrieval or in the absence of retrieval had no effect on drug reward memory and the expression of CPP. SO2 itself did not produce aversive effects nor did it acutely block morphine CPP. Our results indicate that exogenous SO2 impairs reconsolidation of drug reward memory rather than inhibits the expression of drug reward memory. As such, SO2 holds potential for the treatment and prevention of SRADs and should be studied further.
Subject(s)
Behavior, Animal/drug effects , Cocaine/pharmacology , Memory Consolidation/drug effects , Morphine/pharmacology , Reward , Sulfites/pharmacology , Sulfur Dioxide/pharmacology , Animals , Cocaine-Related Disorders/drug therapy , Cocaine-Related Disorders/psychology , Conditioning, Classical/drug effects , Humans , Mice, Inbred C57BL , Morphine Dependence/drug therapy , Morphine Dependence/psychology , Time FactorsABSTRACT
Objective To investigate the role of neuropeptide trefoil factor 3 (TFF3) in cocaine reward responses and the underlying mechanism.Methods Fifty SD rats were divided into 6 groups including Control group,Cocaine group,Cocaine + TFF3 (0.01 mg/kg) group,cocaine + TFF3 (0.1 mg/kg) group,cocaine + TFF3 (0.5 mg/kg) group and TFF3 (0.1 mg/kg) group,ip,n=7 ~ 9),and were treated with TFF3 / saline (ip),30 min later,rats were injected with cocaine (10 mg/kg ip) followed by 1 h hypedocomotion test.Immediately after behavioral test,rats (n=4~6) were decapitated and tissues of nucleus accumbens (NAc) were isolated and prepared for neurotransmitters analysis by HPLC; Another twenty one rats were divided into control and TFF3-treatment group,and the rats were trained with a modified 2-day cocaine CPP conditioning procedure.During cocaine CPP conditioning process,saline or TFF3 (0.1 mg/kg ip) was injected 30 min prior to cocaine injection (5 mg/kg ip).Results Systemic administration of TFF3 (0.1 mg/kg,ip) significantly increased the cocaine-induced locomotor activity (Total distance in 1 hour were (180±41) cm,(359±53) cm,(590±75) cm,(153±27) cm for Control,Vehicle + Cocaine,TFF3+Cocaine and TFF3+Vehicle groups respectively) and augmented cocaine rewarding effects in CPP(Post-training CPP score were (98± 18) s,(187±24) s for Vehicle + Cocaine,TFF3+Cocaine groups respectively).TFF3 (0.1 mg/kg ip) administration increased the dopamine concentration in the NAc induced by cocaine injection ((0.65±0.1) ng/ml,(1.24±0.14) ng/ml,(1.75±0.23) ng/ml,(0.74±0.21) ng/ml for Control,Cocaine,TFF3 + Cocaine and TFF3 + Vehicle groups respectively).Conclusion TFF3 is involved in regulation of behavioral response to cocaine,which is associated with the increasing of dopamine in the NAc.
ABSTRACT
Objective To explore the effects of lactational maternal stress on neurobehavioral development of offsprings.Methods Maternal mice were divided into normal control,maternal deprivation and maternal stress group.A 5-min/day cold water swimming was used as maternal stress for continuously of 14 day since the 7th postnatal day.The increasing bodyweight and neurobehavior of adolescent offspring mice were assessed by forced swimming test,tail suspension test and locomotor activity in the 35th postnatal day.Results Maternal chronic stress in lactational stage significantly increased the vulnerability of offspring to acute stress,which was reflected by significantly increased immobility time of adolescent offspring in forced swimming test (female:(139±6) s,(138±9) s,(96±9) s respectively; male:(139±9) s,(112±9) s,(96±9) s respectively) and in tail suspension test (femal:(127±8) s,(123±8) s,(98±6) s respectively ; male:(141 ±7) s,(105±5) s,(92±6) s respectively).Meanwhile,sexual difference occurred for adolescent offspring to acute stress,and the female offspring were more vulnerable to acute stress.Conclusion Lactational maternal stress may be important factors for development of adolescent depression.Our findings highlight the area of early prevention and intervention for adolescent depression.
ABSTRACT
Objective To determine the affinities of five oligopeptides specifically binding with DNA binding domain of NF-?B p65 subunit and identify their inhibiting effect on DNA binding activity of NF-?B. Methods By using biosensor the affinities were measured by means of kinetic analysis, and the inhibiting effects were determined by competitive ELISA. Results The results of biosensor showed that all of five oligopeptides really possessed the capability of specific interacting with NF-?B p65 subunit. The affinity constants of these oligopeptides were 2.67?10~ -7 mol/L, 9.02?10~ -6 mol/L, 1.07?10~ -6 mol/L, 8.03?10~ -6 mol/L, 9.83?10~ -7 mol/L respectively. The results of competitive ELISA indicated that five oligopeptides could inhibit NF-?B from binding with ?B motif, and their inhibiting effect depended on their concentration. Conclusion Five oligopeptides that were screened by yeast two-hybrid system method can really interact with p65, and possess the inhibiting effect on DNA binding activity of NF-?B. So it will be possible that these oligopeptides are regarded as model to design and develop novel anti-inflammatory peptide drug targeting NF-?B.
ABSTRACT
In order to meet the requirement of the innovation of higher education and fulfill the ideas of quality-oriented education, Biochemistry department of Hebei Medical University adopts PBL teaching approach.It is shown that PBL teaching approach can stimulate the students' interest and motivation in study,develop their self-study ability,activate their mind and improve the teaching quality.