Although morphine does not bind to the σ receptor, it has been shown that σ receptor agonists, such as (+)-pentazocine, inhibit morphine analgesia, and σ receptor antagonists enhance morphine analgesia, suggesting downstream involvement of the σ receptor in the actions of morphine. The effects of morphine can be countered with opioid receptor antagonists such as naloxone and naltrexone; the development of tolerance to morphine may be inhibited by NMDA receptor antagonists such as ketamine or dextromethorphan. The rotation of morphine with chemically dissimilar opioids in the long-term treatment of pain will slow down the growth of tolerance in the longer run, particularly agents known to have significantly incomplete cross-tolerance with morphine such as levorphanol, ketobemidone, piritramide, and methadone and its derivatives; all of these drugs also have NMDA antagonist properties. It is believed that the strong opioid with the most incomplete cross-tolerance with morphine is either methadone or dextromoramide. Gene expression
Studies have shown that morphine can alter the expression of a number of genes. A single injection of morphine has been shown to alter the expression of two major groups of genes, for proteins involved in mitochondrial respiration and for cytoskeleton-related proteins. Effects on the immune system
Morphine has long been known to act on receptors expressed on cells of the central nervous system resulting in pain relief and analgesia. In the 1970s and 80s, evidence suggesting that opioid drug addicts show increased risk of infection (such as increased pneumonia, tuberculosis, and HIV/AIDS) led scientists to believe that morphine may also affect the immune system.
Preadolescence may also be defined as the period from 10 to 13 years.The point at which a child becomes an adolescent is defined by the onset of puberty or the beginning of the teenage stage. However, in some individuals (particularly females), puberty begins in the preadolescence years. Studies indicate that the onset of puberty has been one year earlier with each generation since the 1950s.One can also distinguish middle childhood and preadolescence – middle childhood from approximately 5–8 years, as opposed to the time children are generally considered to reach preadolescence. There is no exact agreement as to when preadolescence starts and ends. Hormonal development and the development of secondary sex characteristics
Early puberty begins as the result of the initiation of the pulsatile gonadotropin-releasing hormone (GnRH) secretion by the hypothalamus; the exact mechanism of this initiation is currently unknown and remains under investigation. Pulsatile GnRH secretion results in the pulsatile secretions of gonadotropins Luteinizing Hormone (LH) and Follicle Stimulating Hormone (FSH), which act on the gonads (ovaries in females or testicles in males) to cause increase secretion of sex steroids. In females, the predominant sex steroid released is estrogen and in individuals with testicles, the predominant sex steroid released is testosterone. These sex hormones then lead to the development of secondary sex characteristics. The stages of puberty can be described with the Tanner scale, also known as the Sexual Maturity Rating, which incorporates measurements and characteristics of primary and secondary sex characteristics. For example, genital and breast development, as well as pubic hair growth.