It has been implicated in addictions to alcohol, cannabinoids, cocaine, methylphenidate, nicotine, opioids, phencyclidine, propofol, and substituted amphetamines, among others.ΔJunD, a transcription factor, and G9a, a histone methyltransferase enzyme, both oppose the function of ΔFosB and inhibit increases in its expression. Sufficiently overexpressing ΔJunD in the nucleus accumbens with viral vectors can completely block many of the neural and behavioral alterations seen in chronic drug abuse (i.e., the alterations mediated by ΔFosB). Similarly, accumbal G9a hyperexpression results in markedly increased histone 3 lysine residue 9 dimethylation (H3K9me2) and blocks the induction of ΔFosB-mediated neural and behavioral plasticity by chronic drug use, which occurs via H3K9me2-mediated repression of transcription factors for ΔFosB and H3K9me2-mediated repression of various ΔFosB transcriptional targets (e.g., CDK5). ΔFosB also plays an important role in regulating behavioral responses to natural rewards, such as palatable food, sex, and exercise. Since both natural rewards and addictive drugs induce the expression of ΔFosB (i.e., they cause the brain to produce more of it), chronic acquisition of these rewards can result in a similar pathological state of addiction. Consequently, ΔFosB is the most significant factor involved in both amphetamine addiction and amphetamine-induced sexual addictions, which are compulsive sexual behaviors that result from excessive sexual activity and amphetamine use. These sexual addictions are associated with a dopamine dysregulation syndrome which occurs in some patients taking dopaminergic drugs.The effects of amphetamine on gene regulation are both dose- and route-dependent.
In later post-eruptive stages GIC may be valuable as sub-layer beneath composite restorations. Indirect restorations
Preformed metal crowns
Pre-formed metal crowns (PMC), also known as stainless steel crowns, can be used to reduce the risk of marginal breakdown, coronal leakage and has a good longevity. The use of preformed metal crowns on MIH-affected molars can prevent further tooth loss, control hypersensitivity and aim to establish correct interproximal and occlusal contact. They are relatively inexpensive and require little preparation.To prevent further tooth preparation and tissue loss, use of the Hall Technique should also be considered. There advantage is use during any stage of post-eruptive breakdown, but evidence of their efficacy is limited. Although the PMC has evidence to show that it is well accepted, a few of the children and their carers expressed their concerns about the metallic appearances of the restoration. Cast restorations
Cast restorations may include full coverage crowns for MIH-affected permanent teeth. Generally cast restorations requiring tooth preparation are not recommended in young children due to large pulp size, short crown height and potential difficulties in obtaining a good impression for subgingival crown margins. Extractions
A list of considerations can affect the final decision on whether extraction of the affected teeth should be carried out or should it be retained such as: severity of MIH; patient’s aesthetic expectations; whether the patient is suitable to undergo orthodontic treatment; orthodontic concerns (e.g. crowding, facial profile, missing or supernumerary teeth, presence of third molars).Timely extractions are often the preferred treatment plan for first permanent molars that are severely affected and symptomatic.