Term
| how does the firing of monoaminergic neurons in the Raphe nucleus, the locus coeruleus and the TMN change between waking, NREM and REM states? |
|
Definition
| they fire fastest during waking, slow down in NREM and essentially stop firing during REM |
|
|
Term
| cholinergic projections from the LTD/PPT fire most during ____________, some during ____________ and not at all during ______________ |
|
Definition
|
|
Term
| true or false: the cholinergic neurons in the LDP/PPT are inhibited by the rapid firing of monoaminergic neurons |
|
Definition
| false, the cholinergic neurons are inhibited by the monoaminergic neurons when they are firing at moderate rates (ie during NREM sleep) |
|
|
Term
| projections from what 5 nuclei make up the ascending arousal system? |
|
Definition
| the locus coeruleus, TMN, raphe nucleus, LTD and PPT |
|
|
Term
| sleep-promoting neurons of the _______________ contain GABA and ___________ |
|
Definition
|
|
Term
| true or false: NREM is considered a readily reversible state |
|
Definition
| false, REM is considered a readily reversible state |
|
|
Term
| GABAergic and Galanergic projections from the VLPO innervate which nuclei? What effect do they have on these nuclei? |
|
Definition
| innervate very heavily the TMN, also innervate the raphe nucleus and the locus coeruleus. have an inhibitory affect on the neurons in these nuclei, lead to sleeping state (not sleepiness) |
|
|
Term
| activation of the locus coeruleus leads to an (awake/asleep) sleep whereas inhibition leads to an (awake/asleep) state |
|
Definition
|
|
Term
| true or false: both alpha-1 and beta dopamine receptor agonists are shown to have a significant affect on waking time (individual spends more time awake when administered) |
|
Definition
| false. these are NE receptors which do have effect on waking time (presence of agonists lead to more time awake) |
|
|
Term
| orexin-releasing neurons are activated by ______________ and ______________ |
|
Definition
| biological clock, hunger signals |
|
|
Term
| true or false: orexin-releasing neurons have projections that lead to all systems involved in arousal and therefore are important in the maintenance of a stable awake state |
|
Definition
|
|
Term
| what are two possible explanations for narcolepsy? |
|
Definition
1. mutations in orexin receptors
2. abnormally low concentrations of orexin present |
|
|
Term
| what two internal processes regulate sleep patterns? |
|
Definition
1. circadian rhythms (regulated by zeitgebers such as sunlight)
2. homeostatic drive (the natureal desire for stability/balance, if dont sleep enough one night want to sleep more the next) |
|
|
Term
| the sleep system is made up of the projections of what type of neurons? where do these neurons originate? |
|
Definition
| GABAergic neurons originating in the VLPO |
|
|
Term
| how do the sleep and arousal systems interact? |
|
Definition
| the GABAergic projections of the sleep system project to all the major ares of the arousal system (raphe nuc, locus coerules, TMN, LDT/PPT) and inhibit their activity |
|
|
Term
| insomnia in rats is observed as the result of the destruction of _________ |
|
Definition
| the VLPO AND SURROUNDING AREAS (get less sleep than normal but not complete insomnia if only destroy VLPO) |
|
|
Term
| what is the role of adenosine in the sleep system? |
|
Definition
| adenosine drives sleep neurons by activating the VLPO and inhibiting the LDT/PPT. adenosine levels build up throughout the day, leading to increased activation of the VLPO which eventually hits threshold and leads to sleep behavior (ind's who dont metabolize adenosine as well need more sleep) |
|
|
Term
| what are two types of drugs that increase drowsiness? |
|
Definition
| anti-histamines and benzodiazepines (GABAa receptor agonists) |
|
|
Term
| what are three types of drugs that decrease drowsiness? |
|
Definition
1. caffeine (adenosine receptor antagonist)
2. psychostimulants (eg cocaine, amphetamine)
3. modafinal |
|
|
Term
| what are the two types of intravenous self-administration (IVSA) tests used on rats? |
|
Definition
1. Fixed Ratio (FR) Schedule- rat must press lever specific # of times to get drug
2. Progressive ratio (PR) schedule- animal required to press lever more times on each subsequent trial to receive reward |
|
|
Term
| _______________ tests allow us to measure the break point (indication of reinforcer effectiveness)and assess motivation |
|
Definition
| progressive ratio schedule |
|
|
Term
| ___________________ tests give us the does-response relationship for a drug |
|
Definition
|
|
Term
| what areas of the brain are principally involved in the brain reward system? |
|
Definition
| cell bodies in the VTA project to the nucleus accumbens and the olfactory tubule |
|
|
Term
| ____________ is the principle active ingredient in opium |
|
Definition
|
|
Term
| what are three different ways to assess the rewarding actions of drug abuse? (hint: animal tests) |
|
Definition
1. Intravenous Self-Administration (IVSA)
2. Intracranial Self-Stimulation (ICSS)
3. Place Conditioning |
|
|
Term
| what does the drug discrimination task tell us? |
|
Definition
| If an unknown drug feels the same (has same effects) as a known drug |
|
|
Term
| codeine has a (higher/lower) affinity for the opioid receptor than morphine |
|
Definition
|
|
Term
| heroine has a (higher/lower) lipid soluabilty than morphine, therefore crosses the BBB (faster/slower) |
|
Definition
|
|
Term
| codeine has (more/less) side effects than morphine |
|
Definition
|
|
Term
| codeine (greater/lesser) analgesic efficacy than morphine |
|
Definition
|
|
Term
|
Definition
| a full competitive antagonist for the opioid receptor (similar in structure to morphine, heroine and codeine) |
|
|
Term
| what are the stages of heroine high? which of these are resistant to tolerance? |
|
Definition
stages:
1. rush (resistant to tolerance)
2. high
3. nod
4. being straight |
|
|
Term
| heroine is converted to ___________ after is crosses the BBB |
|
Definition
|
|
Term
| what are the two different mechanisms of opioid reward? |
|
Definition
1. opium binds to GABA neurons in the VTA, leads to disinhibition of DA neurons in the VTA (?) which project to the NAc (DA-dependent)
2. opium binds directly to MOR and KOR receptors on medium spiny neurons in the NAc |
|
|
Term
| _________ is a neurotoxin that kills catecholamines (eliminates pathway?) |
|
Definition
|
|
Term
| what is crack? how is it made? |
|
Definition
| a psychostimulant made by mixing cocaine salt (HCl) with baking soda, heating then drying it |
|
|
Term
| why can you smoke crack but not cocaine? |
|
Definition
| because crack has a much lower melting point |
|
|
Term
|
Definition
| by making a paste from extraction from leaves of coca plants then converting the paste to a salt and crystallizing it |
|
|
Term
| cocaine is (hydrophilic/hydrophobic) and (lipophilic/lipophobic) |
|
Definition
|
|
Term
| cocaine is metabolized by ____________ to ________________ |
|
Definition
| carboxylesterase (liver enzyme), benzolecgonine |
|
|
Term
| what happens during cocaine binges? |
|
Definition
| euphoria decreases, dysphoria increases, eventually leads to paranoia and stimulant-induced psychosis |
|
|
Term
| cocaine blocks __________, __________, ________ and __________________ |
|
Definition
| DAT, SERT, NET and voltage-gated Na+ channels |
|
|
Term
| what does amphetamine do (on a cellular level)? |
|
Definition
| reverses actions of DAT, SERT, NET and VMAT |
|
|
Term
| true or false: D1-receptor KO mice self-administer cocaine but not food |
|
Definition
| false. self-administer food but not cocaine |
|
|
Term
|
Definition
| fermentation of glucose with yeast (up to 15%), if want higher concentration use distillation (up to 50%) |
|
|
Term
| true or false: alcohol readily crosses cell membranes and the BBB |
|
Definition
|
|
Term
| 20% of alcohol is absorbed through the _________ and 80% through the __________ |
|
Definition
|
|
Term
| what is the effect of alcohol on GABA? |
|
Definition
| enhances GABA transmission in many brain areas, decreases transmission in the VTA |
|
|
Term
| what effect does alcohol have on glutamate? |
|
Definition
| decreases extracelluar GLUT in striatum and other brain areas, NMDA receptor antagonists substitute for alcohol in drug discrimination tests |
|
|
Term
| nicotine is metabolized by ____________ in the ___________ |
|
Definition
| cytochrome P450 2A6, liver |
|
|
Term
|
Definition
| an aldehyde dehydrogenase antagonist given to alcoholics to stop them from drinking (when drink get very sick because cant break down alcohol) |
|
|
Term
| true or false: nicotine can activate receptors in both the sympathetic and parasympathetic nervous system |
|
Definition
|
|
Term
| activation of the sympathetic nervous system and adrenal gland by nicotine leads to release of _____ and ______ |
|
Definition
| epinepherine and norepinepherine |
|
|
Term
| nicotine stimulation of the ___________________ stimulates GI motility and the release of HCl acid by the stomach |
|
Definition
|
|
Term
| nicotine binding to receptors in the _____________ can lead to vomiting in new smokers |
|
Definition
|
|
Term
| nAchR's are (ionotropic/metabotropic) |
|
Definition
|
|
Term
| what is the structure of nAchR's? |
|
Definition
| pentamer with at least 2 binding sites for Ach |
|
|
Term
| true or false: nicotinic ACh receptors are subject to desensitization |
|
Definition
|
|
Term
| alpha4 beta2 receptors have a (high/low) affinity fir nicotine and a (high/low) Ca2+ permeability |
|
Definition
|
|
Term
| alpha7 receptors have a (high/low) affinity for nicotine and a (high/low) Ca2+ permeability |
|
Definition
|
|
Term
| true or false: pretreatment with nicotine increases sujective and pysiological affects of nicotine admin in both smokers and non-smokers |
|
Definition
| false. pretreament decreases the effect of subsequent admin in both populations |
|
|
Term
|
Definition
| an increased responsiveness to a drug or other stimulus with repeated exposures |
|
|
Term
| what are the two phases of sensitization? |
|
Definition
|
|
Term
|
Definition
| a decrease in drug effect with increased drug exposure |
|
|
Term
| _________________ tolerance results from reduced amount of drug reaching target site |
|
Definition
|
|
Term
| ________________ tolerance is a reduced response of neuron to drug |
|
Definition
|
|
Term
| ______________ tolerance is reduced drug effect in specific environment or context |
|
Definition
|
|
Term
|
Definition
| an adaptive state that develops as a result of chronic drug admin, unmasked upon drug discontinuation |
|
|
Term
| ____________ dependence is shown by a somatic signal of withdrawl |
|
Definition
|
|
Term
| ______________ dependence can be shown by dysphoria and anhedonia during withdrawl |
|
Definition
|
|
Term
| what can we determine from a challenge test? |
|
Definition
| if something blocks sensitization of a drug and what neural system is involved in sensitization |
|
|
Term
| in the presence of cocaine there is an increase in phosphorylation of _________ and __________ which leads to _______________________________ |
|
Definition
| CamKII, synapsin, more vesicles in readily releasable pool, more DA released |
|
|
Term
| __________ is important for induction and _________ is important for expression |
|
Definition
|
|
Term
| true or false: addictive drugs do not affect VTA synaptic strength |
|
Definition
| false. non-addictive drugs do not affect synaptic strength |
|
|
Term
| _____________ and ______________can lead to reorganization of neural circuitry that alters gene and protein expression |
|
Definition
| long term potentiation (LTP), long term depression (LTD) |
|
|
Term
| what is the long term potentiation observed with repeated cocaine administration? |
|
Definition
| there is an increase in AMPA receptor expression which leads to increased excitation, high Ca2+ levels and CamKII activation, and an increase in ion flow through the AMPA receptors |
|
|
Term
| cocaine addicts do not show signs of ____________ dependence but do show signs of ___________ dependence |
|
Definition
| physical, motivational/affective |
|
|
Term
| what happens in acute vs. chronic opioid admin? |
|
Definition
| acute admin leads to inhibition of LC neurons. chronic admin leads to upregulation of several components of the PKA pathway |
|
|
Term
| how does the increased excitabilty of LC neurons lead to physical withdrawal symptoms with opioid discontinuation? |
|
Definition
| LC neurons continue to fire at high rate even in absence of drug, leads to physical withdrawal symptoms |
|
|
Term
| true or false: there is a selective inease in creb expression in the LC which leads to affective withdrawal symptoms |
|
Definition
| false. this leads to physical (not affective) withdrawal symptoms |
|
|
Term
| _____________ is a drug given during opiate withdrawal. it is an alpha 2 receptor agonist. |
|
Definition
|
|
Term
| __________ attenuates drug reinstatement by inhibiting glut release to the NAc |
|
Definition
|
|
Term
| ______ and _________ are important for drug-induced reinstatement |
|
Definition
|
|
Term
| DA receptor agonists (attenuate/potentiate) reinstatement in the presence of drug |
|
Definition
|
|
Term
| what are the three human triggers for relapse? |
|
Definition
1. exposure to drug associated cues
2. exposure to stressors
3. exposure to drug itself |
|
|
Term
| inactivation of the _____________ stops context-induced reinstatement |
|
Definition
|
|
Term
| inactivation of the _____________ stops cue-induced reinstatement from occurring |
|
Definition
|
|
Term
| __________ and __________ are important in stress response |
|
Definition
| BNST (bed nucleus of the stria terminus), CEA (central nucleus of the amygdala) |
|
|
Term
| ________ has a central role in stress-induced reinstatement |
|
Definition
|
|
Term
| what role does the PFC play in stress and stress-induced reinstatement? |
|
Definition
| stressers increase activity in the PFC, if block PFC see decrease in stress-induced reinstatement. due to connection between PFC and BLA (which projector to BLST and then VTA) and also direct interactions between the PFC and VTA |
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|
