ABSTRACT
Drug addiction is a chronic relapsing brain disease. Repeated drug exposure can cause neuroadaptations in major brain circuitries,leading to compulsive drug consumption behav-ior and relapse after abstinence.Many studies have found that intercellular signaling cascades mediated central nervous system remodeling in the rewarding circuitry and addiction associated neuroplasticity of learning and memory are important molecular mechanism of drug addiction.Studies show that extracellular sig-nal-regulated kinase (ERK)is associated with drug-mediated psychomotor activity,rewarding properties and relapse of drug seeking behaviors.Therefore,this article has reviewed the role of ERK signaling pathway in drug addiction.Research on the role of ERK signaling pathway in drug addiction will provide im-portant theoretical foundation for in-depth understanding of the molecular mechanism of drug addiction and shine a light on new molecular targets and treatment strategies for drug addiction.
ABSTRACT
Drug addiction is a chronic relapsing brain disease that is characterized by compulsive drug use and persistence of drug craving. Drug abuse can lead to changes in the neuron structure and function of plasticity,alterations in molecules and cells,and ultimately to individual abnormal behavior. Current studies have found that epigenetic changes leading to the sustainability of gene expression is an important mechanism of drug addiction. In this review,we will systematically summarize the latest advances in epigenetic mechanisms of drug addiction. This review is expected to provide robust evidence that repeated exposure to drugs of abuse induces changes within the brain′s reward regions in three major modes of epigenetic regulation-histone modifications such as acetylation and methylation , DNA methylation,and non-coding RNAs. It promises a new perspective from which to gain insights into the genetic and epigenetic mechanisms of drug addiction and a new area for epigenetic research on clinical drug addiction treatment.
ABSTRACT
OBJECTIVE To investigate the effect of injection of β2-adrenergic receptor agonist clenbuterol into the infralimbic cortex(IL) on drug-seeking behavior triggered by conditioned cues. METHODS Adult male SD rats were trained to self-administer heroin under a FR1 schedule for consecutive 14 d,followed by 2-h extinction training. Cue-induced heroin seeking was measured for 2 h. Clenbuterol was microinjected bilaterally into the IL(8 ng/side)of rats 15 min prior to reinstatement test. Meanwhile,locomotor activity was detected 15 min after clenbuterol or artifial cerebrospinal fluid(mod?el group) was microinjected bilaterally into IL. Western blotting was used to detect the expression of phosphorylated cyclic AMP response element-binding protein(p-CREB)in the prelimbic cortex(PL), IL,nucleus accumbens core (NACc) and shell (NACsh) of rats immediately after reinstatement test. RESULTS After heroin administration training for 14 consecutive days,these animals exhibited reliable heroin self-administration,indicated by the increase in active nose poke responses and infusions. The rats that had received infusion of clenbuterol into the IL had significantly lower active pokes (8 ± 3)than those in model group(45±10)in cue-induced reinstatement(P<0.01),but there was no significant differ?ence between clenbuterol group and vehicle group in the locomotor activity. The expression of p-CREB in either IL or NACsh was significantly decreased in clenbuterol group compared with model group(P<0.01,P<0.05),but significantly increased in NACc(P<0.01). CONCLUSION Microinjection of clenb?uterol into the IL can attenuate the cue-induced reinstatement of heroin-seeking behavior in rats. The underlying mechanism might be related to the regulation of p-CREB expression in the NACc and NACsh.
ABSTRACT
The recovery force of Ti-Nb coated and uncoated TiNi shape memory alloy rods was investigated. The rods were 6.0 mm, 6.5 mm and 7.0 mm in diameter respectively. The mean transition temperature was 33.0 degrees C. The rods were stored at -18 degrees C and pre-bent with a three-point bending fixture, the span was 20. 0 centimeters and the deflections were 5.0 mm, 10.0 mm, 15.0 mm and 20.0 mm, respectively. The rods were then heated in a constant temperature saline solution chamber. The experimental temperature was 37.0 C and 50.0 C respectively. The recovery force was measured in a constant displacement mode on biomaterial test machine. The results showed that the recovery force of the memory alloy rod increased with increasing recovery temperature, rod diameter and deformation of both Ti-Nb coated and uncoated surface. The recovery force of Ti-Nb coated rods of 6.0 and 6.5 millimeter in diameter was lower than the uncoated rods in the same diameter. However, the recovery force of 7.0-mm-diameter rods showed no significant difference between coated and uncoated surface.