Classification of drugs Stimulants Amphetamines Caffeine Nicotine Cocaine

Classification of drugs • Stimulants - Amphetamines, Caffeine, Nicotine, Cocaine • Depressants – Analgesics: relieve pain, aspirin or opiates • Narcotics: Opiates such as Heroine, Morphine, Oxycontin, Fentynal • Non-narcotics: Aspirin, etc. – Sedative Hypnotics: relax, induce sedation (see figure 4. 13) • • Alcohol (ETOH) p. 118 not a stimulant Anxiolytics: Anti-anxiety agents, Valium Non-Barbiturates: Qualude, Halcion Barbiturates: Phenobarbital or Seconal • Anti-Psychotics: – Typical: Thorazine or Haldol – Atypical: Clozapine • Anti-Depressants: – MAO Inhibitors: Parnate or Marplan – Trycyclics: Tofranil – SSRIs: Prozac, Zoloft • Neuroactive (Psychogenic) – Hallucinogens: LSD, PCP, Ketamine, Ecstasy – Marijuana – Inhalants – Nitrous Oxide

The GABAA Receptor Has Many Different Binding Sites

Drug Effects • Amphetamine and methamphetamine: release of dopamine, norepinephrine and epinephrine even in the absence of action potentials • Cocaine: increased levels of dopamine because cocaine binds to reuptake mechanism on presynaptic terminal • MDMA (Ecstasy): increases in serotonin levels • Opiates: such as hydrocodone (e. g. , Vicodin), oxycodone (Oxy. Contin, Percocet), bind to opioid receptors Delta (δ), Kappa (κ), Mu (μ) • Marijuana or cannabis: cannabinoids Δ 9 -tetrahydrocannabinol (THC), cannabidiol (CBD) bind to Cannabinoid receptors CB 1, CB 2 • Diazepam (Valium): binds to GABA receptors as an agonist • SSRI fluoxetine (Prozac): blocks reuptake of serotonin • Nicotine: Agonist at the nicotinic acetylcholine receptor

Table 4. 4 Possible Clinical Applications for Hallucinogens Do not need to know this table

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 • • 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

A Neural Pathway Implicated in Drug Abuse

Do not need to know the neuroanatomy Figure 1: VTA–NAc reward circuit. The brain reward circuitry in mood disorders Scott J. Russo & Eric J. Nestler Nature Reviews Neuroscience 14, 609– 625 (2013) doi: 10. 1038/nrn 3381

Neurobiology of addiction: a neurocircuitry analysis • Drug addiction changes motivational circuits in three stages – binge/intoxication stage: exaggerated incentive salience and habit formation • rewarding effects of drugs of abuse produce drug-seeking – withdrawal/negative affect stage: reward deficits and stress surfeits • increased negative emotional states such as dysphoria • decreases in the function of the dopamine component of the reward system – preoccupation/anticipation stage: craving and deficits in executive function • dysregulation circuits from the prefrontal cortex to the basal ganglia

Figure 1: Model of interacting circuits in which disruptions contribute to compulsive-like behaviours underlying drug addiction Do not need to know the neuroanatomy reward craving, impulsivity

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 • Changes to reward pathway – Structural • Dendritic spines • Size of synapses • Receptor density – Molecular Biology (second messenger systems) • CREB • Delta Fos B

Mediators of drug addiction • Experience with addictive drugs such as opiates (morphine, heroin, fentanyl) does not result in addiction in all individuals. – However repeated use increases the addictive potential – Approximately 30 % with opiate drugs • Individual difference – Genetics – Past experiences • • Drugs Stressors Poor coping Lack of social support

Other Addictions? • • Food addiction Sex addiction Gambling addiction Running addiction TV addiction Cell Phone addiction Internet Addiction Addicted To Love