Morphine is one of the most potent alkaloid in opium, which has substantial medical uses and needs and it is the first active principle purified from herbal source. Morphine has commonly been used for relief of moderate to severe pain as it acts directly on the central nervous system; nonetheless, its chronic abuse increases tolerance and physical dependence, which is commonly known as opiate addiction. Morphine withdrawal syndrome is physiological and behavioral symptoms that stem from prolonged exposure to morphine. A majority of brain regions are hypofunctional over prolonged abstinence and acute morphine withdrawal. Furthermore, several neural mechanisms are likely to contribute to morphine withdrawal. The present review summarizes the literature pertaining to neural mechanisms underlying morphine withdrawal. Despite the fact that morphine withdrawal is a complex process, it is suggested that neural mechanisms play key roles in morphine withdrawal.
Introduction
Morphine is the first active principle purified from herbal source (1,2). Investigation on its structureactivity relationship has discovered 200 morphine derivatives (e.g., codeine and related drugs) and synthesis of morphine-derived antagonist drugs (e.g., naloxone, naltrexone and nalorphine) (3). Morphine is a natural product but has high potential for addiction, tolerance, and psychological dependence. It is postulated that physiological dependence develops in several months (4). Morphine receptors are opioid receptors and categorized according to their selectivity in binding and pharmacological assays (5) such as mu-receptors (6) and delta-receptors (7). In addition, of all the classes of opioid receptors, the kappa types are the most complex (8).
Morphine has been traditionally utilized to treat severe and chronic pain (9), for instance myocardial-infraction (MI) pain (10). It suppresses the respiratory activity, and irregular breathing; even so, the main cause of death in morphine poisoning is respiratory depression (3). As a consequence of peripheral vasodilatation, peripheral resistance may decrease. Additionally, morphine declines intestinal secretion and increases intestinal fluid absorption, which inbrings about the constipation (3). High doses of morphine impair finger tapping and the ability of maintaining a low constant level of isometric force (impaired motor control) (11,12). It was also demonstrated that morphine plays a crucial role in learning and memory (13). Passive avoidance learning, which is normally assessed by shuttle box (14), is affected by Morphine (15). Morphine withdrawal syndrome results from adaptations’ response on multiple levels with different mechanism. Although little is known, several neural mechanisms have thus far been shown to be involved in morphine withdrawal. This paper reviews the findings regarding the withdrawal phenomenon and its contributory mechanisms.
Conclusion
Positive and negative reinforcement as key components are present in many types of drug addiction. Continued usage of drug stems from positive reinforcement of drug taking and negative reinforcement results from withdrawal along with quitting drug. The mesocorticolimbic dopamine mechanism, which orginates in the ventral tegmental region and projects to terminal regions such as prefrontal cortex, amygdala, and accumbens, is an important neural network wherein drug-induced neuroadaptations occur, resulting in both types of reinforcement. The reinforcing influences of substance abuse contribute to increased dopaminergic neurotransmission (62) in the Acb (63). Animals lever-press in order to keep increased DA rates over cocaine self-administration (64). However, declined accumbal DA rates are associated with morphine withdrawal (65).
