Drug Addiction

1. Drug Addiction OPIATES

2. Introduction Brief history Neurotransmitters Affected Brain Regions Affected Tolerance, Withdrawal, Behavior

3. Brief History Opiates are drugs derived from the poppy plant Have been used for centuries to relieve pain Includes: opium, heroin, morphine, and codeine Opiates such as morphine and codeine used for medicinal purposes, however can be abused just like opium and heroin.

4. History Continued Opiates also inhibit brain centers controlling coughing, breathing, and intestinal motility. Both morphine and codeine are used as pain killers, and codeine is also used in cough medicine. Opiates depress nerve transmission in sensory pathways of the spinal cord and brain that signal pain. This explains why opiates are such effective pain killers.

5. Neurotransmitters Various Receptors and NTS�s: GABA Endorphins Dopamine Opiate Receptors

6. Neurotransmitters Opiates bind to so-called mu (�) receptors These G-protein-coupled receptors are located on the subsynaptic membrane of neurons involved in the transmission of pain signals.

7. Neurotransmitters GABA Affects dopaminergic cells Opiates and opioid NTS�s activate the presynaptic opioid receptors on GABA neurons This inhibits the release of GABA in the VTA Inhibiting GBA allows the dopaminergic neurons to fire faster

8. Neurotransmitters Endorphins Called natural opiates Involved in glucose regulation Endorphins and Enkephalins are natural neural peptides that bind to opiate receptors to produce euphoric effects Released by brain when exposed to opiates

9. Neurotransmitters Dopamine Dopaminergic cells- dopamine is manufactured, transported down the length of the neuron, and packaged for release in the synapse Key involvement in opioid reward Ventral Tegmental Area known area for DA activity Opioids in VTA have a rewarding affect Effects of opioids are contingent on dopamine activation

10. NeurotransmittersAnimal Studies Dopamine (Agmo et al. 1990) Opioids have an evolutionary purpose Male rats used and partnered with copulatory females Rays administered nalexone, a synthetic opioid It is suggested that release of endogenous opioids renders ejaculation rewarding Dopamine thus seems to be of slight importance for that effect of copulation

11. Neurotransmitters Dopamine opiates applied to the VTA increases dopamine activity. dopamine affects the rewarding properties of opioids in the VTA morphine enhances the firing frequency of mesolimbic DA neurons projecting from the VTA , which provides evidence that opioids have an excitatory affect on dopamine. Dopamine antagonists, molecules that bind to the receptor and prevent it from being activated, block the effect of opioids by halting morphine-induced activities

12. Neurotransmitters Opiate Receptors Presynaptically inhibit transmission of excitory pathways Pathways include acetylcholine, the catecholamines, serotonin, and substance P* *Substance P is a neuropeptide active in neurons which mediate our sense of pain

13. Neurotransmitters Opiate Receptors Proteins found in the brain, where naturally occurring opioids bind to (i.e..endorphins) Opioids mimic these naturally occurring opioid-like molecules that are made and used in the brain Four types of opiate receptors: mu, delta, epsilon, kappa Naltrexone, an opioid blocker that is being used for addiction

14. Brain RegionsLocalization of Opiate Binding sites The VTA includes accumbens caudate nucleus thalamus

15. Brain RegionsOpiates binding to opiate receptors in the NAC: Increase dopamine release 3 neurons in opiate action Dopamine terminal Postsynaptic cell Other terminal(GABA)

16. The Neural Circuit The Reward Pathway Major structures the ventral tegmental area the nucleus accumbens prefrontal cortex Other areas include arcuate nucleus Amygdala locus coeruleus periaqueductal gray area

17. Tolerance Tolerance can be defined as the decreased potency of a drug, such that progressively larger doses must be used to achieve the same effect Dependence, which is closely associated with tolerance, involves a continued need for opioid administration in order to prevent withdrawal symptoms symptoms include nausea, gastrointestinal disturbances, chills, and a general flu-like state in humans Lesion studies indicate that no single brain structure is responsible for the withdrawal symptoms

18. Withdrawal (Caille et al. 2003) Opiate withdrawal has been correlated with decreased extra-cellular dopamine levels in the nucleus accumbens (NAC) of morphine-dependent rats. The authors tested the hypothesis that DA transmission plays a critical role in the induction of motivational and somatic withdrawal symptoms.

19. Behavior Opiates and other neurotransmitters affect behavior and feelings by opening and closing ion channels that control the firing of nerves The drug produces relaxation, relief of pain and anxiety, decreased alertness, impaired coordination and serious problems with constipation. Continued use may result in weight loss, mental deterioration and death. Withdrawal sickness will occur if the drug is discontinued. Overdose can result in stupor, coma and death.

20. StudiesFuture Implications (Segall et al. 1989) found that when naloxone was administered, eating palatable foods was effectively decreased. Shows possible reward systems for anorexia that reaffirm the behavior important implications for the use of opioid antagonists in weight-loss programs

21. Conclusion One of the most detrimental side effects of opium is addiction Opium addiction occurs very rapidly, sometimes within weeks Continued use of the drug occurs not only for the purpose of intoxication, but too avoid the painful side effects associated with withdrawal that naturally come with opiate addiction Thus, more studies should be done on synthetic opiates (I.e. naloxone) in order to aid in overcoming addiction

22. Interesting Fact Unlike the information portrayed in the popular sitcom Seinfeld You would have to ingest 10 lbs. of poppy seeds in order to feel any opiate like effects, or even test positive for drugs such as heroin