Neurobiology of Addiction Flashcards
Mesolimbic Pathway
tract of neurons originating in Ventral Tegmental Area (VTA) and terminating in Nucleus Accumbens (NaC)
final common pathway for reward/ pleasure seeking
-stimulated ->dopamine
drug use releases more than natural rewards
Endogenous / exogenous Drugs
Brain makes own morphine (beta endorphin) and it’s own marijuana (anandamide)
also makes its own anxiolytics, antidepressants, & hallucinogens
DEA Classifications of Drugs
**Does not include alcohol/ nicotine
Schedule I-high potential for abuse/ no current accepted medical use- heroin, LSD, cannabis, peyote, quaalude, MDMA
Schedule II-high potential for abuse/ dependence but with medical use-dilaudid, methdone, oxycodone, Demerol, amphetamines, and barbiturates
Schedule III-less abuse potential than I & II. combo products <15mg (vicodin), <90mg codeine (tylenol with codeine), buprenorphine, ketamine, anabolic steroids
Schedule IV-lower potential for abuse (benzos)
Schedule V-low potential for abuse (robitussin or phenergan with codeine)
Stress-Diathesis Theory/ Two-Hit Hypothesis
for addiction to manifest, 1) internal/ genetic predisposition & 2) external/ environmental stimulus
genetic factors
estimated 40-60% of vulnerability is attributed to genetic factors
- assoiciation found between alcohol & genes for specific GABA receptor production
- polymorphisms of dopamine type 2 receptor have been linked to higher vulnerability of drug addiction
Changed Set Point Model
Based on altered neurobiology of a) dopamine neurons in VTA, b) norephinephrine neurons in locus coeruleus (LC)
Variant #1 - release of dopamine reduced to natural rewards/ norephinephrine increased during withdrawal
Variant #2 - resting levels of dopamine altered due to a) glutamate & b) autoreceptors/ increased autoreceptors + dopamine deprivation + pain, malaise, agitation
Variant #3 - emphasizes environment sensitivity to cues d/t cravings in response to increase glutamate/ norephinephrine
Cognitive Deficits Model
abnormalities in prefrontal cortex
- normally, PFC sends inhibitatory signals to VTA of mesolimbic reward system to overcome impulses
- stimulant drugs appear to damage this tract (frontostriatal loop)
- chronic alcoholics have abnormally low levels of GABA, the neurochemical that the PFC uses to signal reward system to release less dopamine
Drugs & Neurotransmitters
Alcohol = GABA & glutamate NT system
THC = cannabinoid receptor
Opiates = mu-opiate receptors
Nicotine = acetylocholine system & nicotine receptors
Hallucinogens = serotonin (5HT) receptors
Phencyclidine / PCP= glutamate
psychostimulants (meth, cocaine, amp) = terminal neurons in NAc / increased dopamine
Cortisol
Cortisol raises level of activity in mesolimbic reward system
Absorption
process of drug movement from site of drug delivery to the site of action
ex. orally, intranasally, smoked, IV transdermally
distribution
once absorbed, the distribution to the various organs & tissues of the body
- influenced by organ perfusion, organ size, binding of drug, and permealbility of tissue
- most psychoactive drugs enter brain bc highly lipid soluble
Metabolism
process of chemical modification of drugs by the body; generally into inactive or less active compounds
pharmocokinetics
study of the time course of drug concentrations determined by absorption, distribution, metabolism, and elimination
Pharmalogical effect
magnitude depends on the free (unbound) drug concentration and it’s site of action
pharmacogenomics
study of the relationship between genetic variations and drug distribution & response
