Download Fig 4.9a Synaptic Transmission

Most drugs affect synaptic transmission
Figure 4.10 Drug Effects on Presynaptic Mechanisms
Figure 4.11 Drug Effects on Postsynaptic Mechanisms
GABA Ionophore with several binding sites that enhance or inhibit GABA’s
effects
Figure 4.12 The GABAA Receptor Has
Many Different Binding Sites
Classification of drugs
• Stimulants
– Amphetamines, Caffeine, Nicotine, Cocaine
• Depressants
– Analgesics: relieve pain, aspirin or opiates
• Narcotics: Opiates and Opioids, Heroine or Morphine
• Non-narcotics: Aspirin, etc.
– Sedative Hypnotics: relax, induce sedation
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Alcohol (ETOH)
Anxiolytic Anti-anxiety agents, tranquilizers: Valium
Non-Barbiturates: Qualude, Halcion
Long acting Barbiturates: Phenobarbital
Short acting Barbiturates: Seconal
Anti-Psychotics: Thorazine
Anti-Depressants: Prozac, Lithium
Hallucinogens: LSD, PCP, Ecstasy
Marijuana
Inhalants
Amphetamine and methamphetamine
• synthetic stimulants that resemble catecholamines in
structure.
• cause the release of catecholamines neurotransmitters
– dopamine, norepinephrine and epinephrine even in the absence of
action potentials
• Short-term effects
– alertness, euphoria, and stamina
• Long-term use
– sleeplessness, weight loss, and schizophrenic symptoms.
Cocaine
• Stimulant derived from cocoa shrub
• Acute effects
– Stimulant: Increased levels of dopamine because
cocaine binds to reuptake mechanism on presynaptic
terminal dopamine can not be removed from the
synapse
• Chronic effects
– addiction
• Dopamine neurons adjust
• Particularly evident in the rewards circuits
• Changes to neuron structure and neurobiology
MDMA (Ecstasy)
• Hallucinogenic amphetamine derivative
– Acute effects
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increases in serotonin levels
Calming
Euphoria
Sense of Well Being
– Chronic effects
• damage to serotonin-producing neurons
• Cognitive effects including memory and attentional
problems
Opiates
• Exogenous: Opium (extracted from poppy seeds)
• contains morphine, an effective analgesic and is highly addictive
• Medications such as hydrocodone (e.g., Vicodin), oxycodone
(OxyContin, Percocet), and codeine are commonly used as drugs of
abuse
• Endogenous opiates are also addictive:
• Enkephalins
• Endorphins
• Dynorphins
• Bind to opioid receptors especially in the locus
coeruleus and the periaqueductal gray.
• three main types of opiate
• Delta (δ)
• Kappa (κ)
• Mu (μ)
• Nicotine modulates this dopamine neuron several different ways
– nicotinic receptors on the actual dopaminergic neuron when nicotine
binds to that receptor, it turns the dopamine cell on
– nicotine stimulates glutamatergic inputs, which are excitatory on the
dopamine neuron which leads to more dopamine being released
– nicotine stimulates GABAergic neurons
• Which inhibits the reward system
• however after chronic exposure to nicotine this cell desensitizes so there is less
inhibition leading to even more dopamine being released
Addictive Drugs
• Characteristics of Addictive drugs
– voluntarily self administered
– enhance (directly or indirectly) dopaminergic synaptic
function in the nucleus accumbens (NAC)
– stimulate the functioning of brain reward circuitry
(producing the “high” that drug users seek
– functionally these circuits are involved in
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regulation of hedonic “pleasurable” quality
encoding attention
reward expectancy
incentive motivation
Short-term VS Long-term Effects of Drugs
• Short term, acute effects
– Immediate action of drug binding to receptors
– Cocaine increases dopamine levels which
produces stimulation
• Long term, such as drug tolerance, addiction
– Neurons change because of drug exposure
• neuroplasticity to drug and its effects
– at dendrites, pre & post synapse, receptors
– changes to anatomy and chemistry
• neurotoxicity: damage to neurons
Reward Pathway
• Ventra Tegmental Area (VTA) to Nucleus Accumbens (NA)
• Release of Dopamine at NA
• VTA circuits
– Are inhibited by GABA via local circuits
– Get input from hypothalamus, frontal cortex
• NA circuits
– Excited by Dopamine, Glutamate, Opiates
– Input from limbic system and frontal cortex
• Role of mesolimbic dopamine (DA) systems to reward could
be from
– Liking: the hedonic impact of reward
– Learning: learned predictions about rewarding effects
– Wanting:
• the pursuit of rewards by attributing incentive salience to reward-related
stimuli
• supported by a majority of the evidence
Figure 4.21 A Neural Pathway Implicated in Drug Abuse
The Addicted Brain
• Drugs of abuse increase activity of the
reward system
• Chronic drug use
– Structural and biochemical changes
– Decreased pleasure
– Increased craving
– Can last for years
• See figures in Scientific American article
Changes to reward pathway
• Structural
– Dendritic spines
– Size of synapses
– Receptor density
• Biochemistry
– CREB
– Delta Fos B
Other Addictions?
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Food addiction
Sex addiction
Gambling addiction
Running addiction
TV addiction
Cell Phone addiction
Internet Addiction
Addicted To Love