Drugs of Abuse- Linger Flashcards
what is dependence
i) Defined, in part, as the compulsive use of a substance despite significant problems resulting from such use
ii) According to the DSM-IV, to be diagnosed as substance dependent, three of the following criteria must be met in a 12 month period:
(1) Preoccupation with use of the chemical between periods of use
(2) Using more of the chemical than had been anticipated
(3) The development of tolerance to the chemical in question
(4) A characteristic withdrawal syndrome from the chemical
(5) Use of the chemical to avoid or control withdrawal symptoms
(6) Repeated efforts to cut back or stop the drug use
(7) Intoxication at inappropriate times (such as at work), or when withdrawal interferes with daily functioning (such as when hangover makes person too sick to go to work)
(8) A reduction in social, occupational or recreational activities in favor of further substance use
(9) Continued substance use in spite of the individual having suffered social, emotional, or physical problems related to drug use
what is the psychological component of dependence
(1) Dependency of the mind that can lead to psychological withdrawal symptoms (such as cravings, irritability, insomnia, depression, anorexia, etc)
(2) Similar to the neurotic behavior patterns of the persistent coffee drinker or cigarette smoker
(3) When drug use becomes compulsive, physiologic dependence and tolerance are likely to develop
physiological (physical) component of dependence
(1) An altered physiologic state that requires continuous drug administration to prevent an abstinence or withdrawal syndrome
(2) Withdrawal syndrome is characterized by states of increased anxiety, insomnia, and CNS excitability that may progress into convulsions in the case of sedative-hypnotics or ethanol
what is abuse and what criteria define abuse
i) According to the DSM-IV, abuse is defined as a pattern of substance use leading to significant impairment in functioning
ii) Of the nine criteria listed above for dependence, only one must be present in a 12 month period
what is addiction
i) Essentially the same definition as psychologic dependence, but addiction is a more outdated term
ii) Consists of compulsive, relapsing drug use despite negative consequences, at times triggered by cravings that occur in response to contextual clues
iii) Genetic component: the relative risk for addiction (addiction liability) of a drug correlates with its heritability, suggesting that the neurobiologic basis of addiction common to all drugs is what is being inherited
what is tolerance
i) A decrease in responsiveness to a drug following repeated exposure
ii) The dose response curve shifts to the right
iii) May be due to pharmacokinetic changes (reduction in drug concentration or shorter duration of action due to changes in drug metabolizing enzymes) or pharmacodynamic (changes in receptor function)
iv) Example drug: diazepam
what is sensitization
i) An increase in response with repetition of the same dose of the drug (also known as reverse tolerance)
ii) Conditioning is a form of sensitization
iii) The dose-response curve shifts to the left
Example drug: cocaine (repeated daily administration of cocaine to rats produces an increase in motor activity that increases over several days even though the dose remains constant
what is withdrawal
i) Consists of adaptive changes that become fully apparent once drug exposure is terminated
ii) The only actual evidence of physical dependence
iii) Generally due to readaptation of the CNS to the absence of the drug of dependence
iv) Example: decreased expression of GABAA receptors and increased expression of NMDA receptors due to chronic ethanol exposure causes hyperarousal of the CNS during ethanol withdrawal
what is the prime target for addictive drugs
the mesolimbic DA system
ii) Originates in the ventral tegmental area (VTA), a tiny structure at the tip of the brainstem, which projects to the nucleus accumbens, the amygdala, the hippocampus, and the prefrontal cortex
iii) Most projections of the VTA are DA-producing neurons: large quantities of DA are released in the nucleus accumbens and the prefrontal cortex when the DA neurons of the VTA are activated
iv) As a general rule, all addictive drugs activate the mesolimbic DA system
where do neurons in the mesolimbic dopamine system project?
originate in the VTA
project to nucleus accumbans prefrontal cortex amygdala hippocampus
what is the dopamine hypothesis of addiction
i) Dependence-producing drugs activate the mesolimbic DA system, releasing DA
ii) The pleasure-related (hedonic) effect results from activation of this pathway, rather than from a subjective appreciation of the diverse other effects (such as alertness or disinhibition) that the drugs produce
iii) Numerous scientific studies support this hypothesis
(1) Deletion of dopamine D2 receptors in mice eliminates the reward properties of morphine without eliminating other opiate effects
(2) D2 receptor deletion does not prevent the occurrence of physical withdrawal symptoms in morphine-dependent animals, suggesting that the dopaminergic pathway is responsible for the positive reward but not for the negative withdrawal effects
what are the 3 molecular targets of addictive drugs
(1) Gio-coupled receptors
(2) Ionotropic receptors (ion channels)
(3) Monoamine transporters
which drugs have the highest (4-5 rating) rating of addiction)
opioids
nicotine
cocaine
amphetamine
which drugs activate G-protein coupled receptors
Opioids - mu (Gi)
cannabinoids (Gi)
GHB (gamma-hyroxybutyric acid)
LSD, mescaline, psilocybin
which drugs activate ionotropic receptors and ion channels
nicotine - nAChR - agonist
alcohol (GABA, 5-HTR, nAChR, NMDA)
benzodiazepines (GABA) positive modulator
Phencyclidine, ketamine (NMDA) - antagonist
which drugs bind to transporters of biogenic amines
Cocaine (DAT, SERT, NET)- inhibitor
Amphetamine (DAT, NET, SERT, VMAT) - reverse transport
Ecstasy (SERT>DAT, NET) - reverse transport
what is the target of nonaddictive drugs of abuse
a) Nonaddictive agents primarily target cortical and thalamic circuits rather than the mesolimbic dopamine system and therefore alter perception without causing sensations of reward and euphoria
which drugs are considered non addictive
lysergic acid diethylamine (LSD) , mescaline, psilocybin
Phencyclidine (PCP) and ketamine
i) Lysergic acid diethylamine (LSD), mescaline, psilocybin
effects?
(1) Repetitive exposure leads to rapid tolerance (tachyphylaxis)
(2) Animals will not self administer hallucinogens, suggesting they are not addictive in nature
effects of PCP and ketamine
(1) Developed as general anesthetics (ketamine is still used for this purpose)
(2) Club drugs sold under names such as angel dust, Special K, Hog
(3) Psychedelic effects last for about 1 hour and also include increased blood pressure, impaired memory function, disorientation, nystagmus, and visual alterations
(4) Classification of these NMDA antagonist as nonaddictive agents has been questioned due to animal research that shows that PCP can increase mesolimbic dopamine concentrations and has some reinforcing properties in rodents
