PREVENTION STRATEGIES MEDICALLY INDUCED ADDICTION

Drug addiction is a chronic disease characterized by compulsive drug use despite the severe negative consequences associated with it. Repeated exposure to drugs of abuse results in molecular adaptations in neuronal signaling pathways, which eventually manifest in the complex behavioral alterations that characterize addiction.

 

OXT on learning and memory processes and the emerging conceptualization of addiction as ‘pathological learning’ have contributed to the demonstration that OXT effectively attenuates long-term neuroadaptation related to opiate and psychostimulant addiction. Through integrating earlier evidence with recent discoveries of the social/affiliative role of OXT, we propose that OXT may interfere with reward and addiction by influencing neurobiological processes involved in stress, learning and memory and social/affiliative behavior

nervous system (CNS). OXT acts within the CNS and has been shown to inhibit the development of tolerance to morphine, and to attenuate various symptoms of morphine withdrawal in mice. In rats, intravenous self-administration of heroin was potently decreased by OXT treatment. In relation to cocaine abuse, OXT dose-dependently decreased cocaine-induced hyperlocomotion and stereotyped grooming behavior.

outside its classic peripheral endocrine functions. OXT involvement in adaptive central nervous system processes has been demonstrated as an inhibitory, amnestic action on learning and memory in different paradigms. Because adaptation and learning are likely to be involved in the neural events leading to drug tolerance and dependence, the

action of OXT on drug related behavior. Both morphine tolerance and dependence, and cocaine administration, increased dopamine utilization in the mesencephalon and in the nucleus accumbens, respectively. OXT treatment decreased the alpha-methylparatyrosine-induced dopamine utilization in the mesencephalon and in the nucleus accumbens-septal complex. Chronic OXT treatment decreased the number of apparent binding sites of dopamine in the basal forebrain area. It also inhibited a cocaine-induced increase in dopamine utilization in the nucleus accumbens, but not in the striatum.

Therefore, OXT may act as a neuromodulator on dopaminergic neurotransmission in limbic-basal forebrain structures to regulate adaptive CNS processes leading to drug addiction.

. Drug tolerance, dependence andaddiction may involve neuroadaptive mechanisms related to learning and memory at cellular and systems levels.

Interaction of OT with dopaminergic neurotransmission in the nucleus accumbens, a key brain structure in drug addiction, as well as OT-ergic regulation of hippocampal processes may be among the mechanisms of action through which OT modulates neuroadaptation to cocaine.

preclinical studies have illustrated a remarkable ability of exogenously delivered oxytocin to inhibit stimulant and alcohol self-administration, to alter associated drug-induced changes in dopamine, glutamate and Fos expression in cortical and basal ganglia sites, and to prevent stress

Chapter 4The NMDA Receptor and Alcohol Addiction

 

consequences; it is thought to be associated with aberrant learning and memory processes . The NMDA-type glutamate receptor (NMDAR) plays an essential role in synaptic plasticity and learning and memory. Not surprisingly, it is well established that the NMDAR is a major target of alcohol (ethanol) in the brain and has been implicated in ethanol-associated phenotypes such as tolerance, dependence, withdrawal, craving, and relapse .

in human trials as potential drugs that alleviate adverse phenotypes that are associated with alcoholics. For example, administration of the NMDAR antagonist, ketamine, to recovering alcoholics reduced psychosis, negative symptoms, dysphoric mood, and worsening of cognitive function [141]. A recent study showed that the well-tolerated NMDAR antagonist memantine [142] reduced alcohol-induced cue-induced craving [143], suggesting that well-tolerated NMDAR antagonists such as memantine could potentially be used as medications for the treatment of alcohol addiction.

Interestingly, various studies suggested that acamprosate modulates the activity of the NMDAR. Acamprosate was shown to act as a weak antagonist [144] or a partial “coagonist” at the NMDAR, so that low concentrations enhance activation when receptor activity is low, whereas higher concentrations are inhibitory to high levels of receptor activation [145 reward circuitry. In the last several decades, however, it has become apparent that glutamatergic transmission plays a pivotal role in addiction and thus may be a key target for possible novel pharmacological treatments [13,14

 

pharmacology, and signaling mechanisms. Glutamate synthesis, metabolism, receptor trafficking, signaling, and excitatory transmission are crucial components for normal brain functioning [15]. With regard to the mesolimbic dopamine reward circuitry, there are numerous glutamatergic innervations from distinct cell populations to the nucleus accumbens (NAcc), amygdaloid complex (Amyg), ventral tegmental area (VTA), and frontal cortex (FC) (for a review see [13]). The N-methyl-d-aspartate (NMDA) receptor is one of three types of iGluRs, and is critically involved in numerous neuronal and brain functions including fast excitatory transmission, synaptic plasticity, learning, and memory [16,17,18,19].

synapse to increase the functioning and efficiency of neurotransmission. Synaptic plasticity and LTP are critical for processes related to learning and memory [18,20]. Abnormal functioning of the NMDA receptor is theorized to

These studies demonstrated that NMDA antagonists block the rewarding or reinforcing effects of drugs of abuse such as morphine and cocaine [35,36].

PCP (see Figure 1) [31]. Memantine is considered an “uncompetitive antagonist” since it binds to the receptor channel rather than the extracellular glutamate binding site [38]. In addition to its antagonist actions at NMDA receptors, memantine also blocks the type 3 serotonin (5-HT3) receptor as well as nicotinic acetylcholine receptors [9]. Memantine has been shown to block NMDAR activity in the presence of prolonged elevations of glutamate concentrations, but it is not as active when glutamate levels increase for shorter periods of time, as in synaptic transmission [26]. Some studies have suggested that memantine preferentially blocks extrasynaptic NMDAR channels while sparing normal synaptic activity, which may underlie the general tolerability of memantine. Unlike other NMDA antagonists such as ketamine or dextromethorphan, memantine does not appear to have abuse

Preclinical Findings

Studies in mice and rats have shown that memantine attenuates the acquisition or maintenance of intravenous self-administration of morphine, nicotine, or cocaine

PREVENTIVE STRATEGIES FOR MEDICALLY INDUCED DRUG ADDICTION:

 

INTRODUCTION:

People may get addicted to a drug ,prescribed for some medical purpose.  A neurobiological model of addiction has proposed cellular adaptation as mechanism of drug addiction. Excessive release od dopamine in NA due to drug intake produces euphoric sensation leading to pathological learning. .Repeated use of drug increase glutametergic drive from prefrontal to NA cause compulsive seeking of drug in drug addicts .Is it possible to prevent medically induced addiction.

Method:

.

Pub med search was made by using key words , addiction model, dopamine ,glutamate ,anticraving medicine, oxidative stress.

 

RESULTS:

Different anti glutametergic medication like ketamine, mementine, accomprosate modulate glutamatic excitation to prevent addiction. Natural medicine like N acetyle cystine and oxytocin may have protective role in addiction. . Typical antipsychotic can block surge of dopamine in NA.

 

Discussion :

 

When addictive drug has to be used inevitably for medical purpose it should be combined with other drugs to prevent development of addiction. First euphoria related to dopamine release in NA  can be blocked by use of low dose typical antipsychotic or dopamine partial antagonist .. NMDA is molecular target of various addictive drugs. Memtentine, ketamine or accomprosate can minimize effects of glutametergic plasticity. N accetyle cystine can restore glutamatergic pathway by its system of cystine- glutamate antiporter.It is source of glutathione largest anti oxidant system of body. Intranasal oxytocin can prevent addiction through its action on  stress ,,learning, memory and intimacy. I

 

CONCLUSION:

 

Different strategies can be used to prevent medically induced addiction