Drugs Behaviours Flashcards
psychostimulants
indirect DA agonists = cocaine, amphetamine, methamphetamine, methylphenidate (ritalin)
cocaine
found in leaves of coca shrub. schedule I drug (but can be used as local anaesthetic). can be taken orally, intranasally, IV, smoked (most cocaine destroyed by heat) but usually snorted. one of the most highly abused drugs is crack cocaine. peak effect around 5 minutes. half life about 15 minutes. alcohol converts cocaine into cocaethylene (easily OD). effects of cocaine not as strong with highly functional individuals.
- physiological effects: increases heart rate and blood pressure, appetite suppressant
- behavioural/subjective effects: High (mood elevation, euphoria), rush (great pleasure), hyperactivity (increased aggressiveness). - happens very quickly
amphetamine
synthetic psychostimulant. plant compound similar molecular structure called khat (can chew). extract compound from khat - bath salts. amphetamines used to treat narcolepsy. long half life when smoked. methamphetamine and MDMA (ecstasy) members of the same family. schedule I drug. can be taken orally or IV. physiological, behavioural/subjective effects similar to cocaine. neurotoxicity high for meth. neurons themselves are dying. reduction in serotonin transporters. effects of MDMA reversible. stress response sensitized for a longer period of time.
cocaine and amphetamine
repeated use results in tolerance and sensitization depending on dose and frequency. tolerance reduces risk of overdose. if drug is readily available can lead to binge stage. no physical symptoms for withdrawal. episodic craving during period of extinction.
mechanism of action of cocaine
cocaine acts by blocking the reuptake of DA, NE, 5-HT. cocaine blocks 5-HT reuptake most effectively. cocaine’s effects on locomotor activity, reinforcement, addiction are mediated by DA system. can block voltage gated sodium channels and block action potentials - why it acts well as a local anaesthetic.
mechanism of action of amphetamine
acts by blocking reuptake of DA, NE, 5-HT and the effects on locomotor activity, reinforcement, addiction are mediated by DA system. blocks DA reuptake most effectively. releases DA from the vesicles and reverses effects of DAT. goes through the transporters, gets into synapse and reverses activity of DAT - releases DA instead of removing DA. blocks reuptake of DA through DAT and increases DA release into synaptic cleft to be diffused into cytoplasm.
the DA system
includes 2 major neuronal pathways: nigrostriatal (substantia nigra to dorsal striatum/caudate putamen) and the mesocorticolimbic (ventral tegmental area to ventral striatum/nucleus accumbens and PFC = considered the major pathway). nigrostriatal involved in motor performance. mesocorticolimbic more involved in hyperactivity seen with cocaine and amphetamine and in the reinforcing effects. VTA and substantia nigra important in reinforcing effects of cocaine in self admin.
- Use neurotoxin = 6-OHDA /6-hydroxyldopamine - to destroy specifically dopaminergic neurons and therefore create Parkinson’s by injecting directly into substantia nigra.
role of DAT in cocaine effects
DAT knockouts still get this increase in cocaine intake - also show hyperactivity when given cocaine without DAT. almost impossible to survive without a functioning dopaminergic systems yet those mice somehow survived - adapted and survived because brain changed. this adaptation was that norepinephrine receptor took over instead of DAT and serotonin transporter was modified. in both DA and 5-HT knockout, dont see an increase in cocaine intake. amphetamine works differently than cocaine.
DA receptors
two subtypes = D1-like (D1 and D5 - Gs) and D2-like (D2, D3, D4 - Gi). D1-like activate adenyl cyclase which converts ATP into cAMP which interacts with protein kinase A which interacts with CREB. this interaction causes the increase in expression of genes. D2-like inhibits adenyl cyclase so theres less cAMP, less CREB activated and less genes expressed. all dopamine receptors are GPCRs. blocking specifically D1 = decrease in locomotor activating effect and reinforcing effects (self admin) of psychostimulants
Mesocorticolimbic circuits
ventral striatum/nucleus accumbens receives input from the PFC, hippocampus, thalamus, amygdala. VTA sends DA input into NAc and the NAc sends GABA output into the VRA. medium spiny neurons send direct information into the VTA. direct pathways express mostly D1 and indirect (stops at ventral pallidum before going to VTA) expresses D1 and D2. DA is called a modulator - released over a wide area, not as targeted, floods the NAc with DA. . NAc important in the control of important functions like learning, motivation, reward seeking.
adaptations in the DA system following chronic drug use (3)
reduction of DA D2 receptors in the striatum, lower DA release in substance users, sensitization of DA release with repeated exposure.
adaptation: reduced D2 receptors
brain adapts following repeated exposure = reduced expression of D2 receptors. D1 receptors are the ones critical for hyperactivity of psychostimulants (important for reinforcing effects of cocaine and others). PET scans of abstinent drug users using raclopride. control has high concentrations of D2 receptors in dorsal striatum and the other group of various users of different substances showed reduced expression of D2 receptors. raclopride is a ligand that attached to DA D2 receptors with good specificity. if there were lots of D2 receptors, there would be an increased signal from raclopride indicating increased density. density of DA receptors seems to be lower indicating brain adapted.
adaptation: lower DA release
DA concentrations are lower. used methylphenidate (MP) - indirect DA agonist - to assess levels of DA in normal and cocaine user brain in a PET scan. when given ritalin (MP) DA levels increased in control. cocaine user had lower baseline of D2 availability before MP was given. There was a reduction in DA release following MP. when theres less DA released, raclopride can bind more readily to DA receptor leading to an increased signal. when theres more DA released, DA and raclopride compete for receptor leading to lower signal. even with MP, there isnt much change in the signal compared to baseline (expected signal to be lower since more DA should be released) indicating that chronic users have less DA release.
adaptation: sensitization of DA release
experiment: exposing regular subjects with amphetamine. expect that amphetamine would increase DA release. got a baseline PET scan to assess density of receptors under normal conditions. multiple scans - after amphetamine, after 3 weeks, after 1 year all with amphetamine. the effect on behaviour increased with the same dose = sensitization. similar effect shown using raclopride binding potential. when the binding potential is lower there is more DA present. results showed that binding potential reduces over repeated doses = sensitization of DA release = more DA released with every repeated dose. sensitization occurs because the brain adapts.
opiates
also known as opioids. opium is the extract of the poppy plant and is the source. used to induce sleep, pain relief, treat diarrhea back then. active ingredients are mostly morphine, then codeine, thebaine. morphine and codeine used to treat pain. morphine is the most commonly prescribed opioid. opium can be smoked, eated, morphine usually injected. heroin is 2-4x more potent than morphine and acts faster (schedule I). heroin taken IV, snorted, injected under skin. heroin itself does not interact with receptors - heroin converted rapidly into 6-monoacteylmorphine (3-10x more potent than morphine) and then slowly converted to morphine in the brain and blood. fentanyl (synthetic, 80x more potent than morphine), oxycodone/oxycontin (synthetic, 1-4x more potent than morphine). chronic users higher potential to get disease.
- physiological effects: decreased body temperature, suppressed cough reflex and breathing centre, nausea, decreased gastro-intestinal secretion and motility, constricted pupils, coma - constipation in chronic users (no tolerance)
- behavioural/subjective effects: low doses = analgesia, higher doses = euphoria, high to nod (sleepiness, unconsciousness) to straight (baseline)
- some effects show tolerance = analgesia, euphoria, sedation, lethal dose.
- severe withdrawal = physical and affective symptoms. physical symptoms peak 36-48 hrs after last dose and up to 72 hrs. most symptoms over within 7-10 days.
