neuropharm exam 3

One of the main cocaine metabolites is ____

also formed when alcohol is ingested along with cocaine _______

Cocaine blocks the reuptake of _____ , _____, and ______ by ______ making cocaine a ______

Order and affinity cocaine binds to each transporter from highest to lowest?

serotonin, norepinephrine, dopamine

Drugs that are used in the treatment of depression are also ________ inhibitors with highly medicinal value, but, unlike cocaine, they do not have ______.

Typical aspects of the cocaine" high“ are feelings of _____ and _____, a sense of ____, ______, ______ and  and great ______.

Cocaine is considered a _____ drug, which means that it produces symptoms of sympathetic nervous system activation.

The physiological consequences of acute cocaine administration include ______ , _____ and ______, and _______;

High doses of cocaine, however, can be toxic or even fatal. Some of the potential adverse consequences of heavy cocaine use are _____, heart failure, _____, or intracranial hemorrhage (due to ruptured artery).

Increased DA release plays a key role in the subjective and behavioral responses (reward responses) to cocaine and other psychostimulants (reinforcing effects) via _____ pathway

Psychostimulant microinjection in the nucleus accumbens  = 

Psychostimulant microinjection in the striatum =

6-OHDA lesion in nucleus accumbens causes ____ locomotor response following systemic administration of a ____ dose psychostimulant

and

_____ reinforcing effectiveness of systemically administered psychostimulants

6-OHDA lesion in striatum causes _____ stereotyped behaviors following systemic administration of _____ dose psychostimulants

amphetamine microinjection in nucleus accumbens is ______ to the animal

cocaine microinjection in the nucleus accumbens is ______ to the animal

Aside from cocaine, another dopamine reuptake inhibitor that blocks dopamine transporters is _______

It is used to treat _____

Prevention of cocaine's enhancement of brain stimulation reward by the D3 receptor antagonist ______

When the prefrontal cortex and/or amygdala respond to emotional stimuli like drug cues, they release GLU and projecting to the midbrain DA neurons. This is the mechanism called _______ that causes the cue-related increase in striatal DA release

On the aspect of cocaine craving: the _____ DA pathway is part of a larger circuit that is activated by chronic cocaine use, which contributes to experience craving for the drug.

longer periods of access to cocaine can lead to 1). ______ that, in turn, 2). _____ the reward circuit (increased threshold). This presumably makes the cocaine _____ and thus supports further increases in _____, which parallels some of the reported findings that reduced cocaine-induced euphoria is accompanied by increased use or even switch to ______.

For the case of cocaine use, tolerance or sensitization depends on the _____ of drug exposure, the _____ that is being measured, and the _____ that has elapsed since the last dose


Continuous cocaine infusion into rats causes _______ to the drug's locomotor-stimulating effect;
Once-daily cocaine injections lead to ______, as shown by enhanced stereotyped behaviors.

two areas of the brain that contribute to cocaine sensitization

drug  (a D2 agonist). for challenge test

Serious health concerns: repeated or high-dose cocaine use can have many adverse physiological and behavioral consequences


4 listed

cocaine 
Pharmacotherapies: Basically, the pharmacological strategy for treating is using DA, NE or 5-HT _____ or _____, or even _____, to compete with cocaine for access to the transporters (mainly DA transporter), thereby possibly blunting the euphoric effects of cocaine-induced dopaminergic stimulation. These drugs would have much less abuse potential than cocaine, because of their lower efficacy at the receptors.

Amphetamine is the parent compound of a family of _____ psychostimulants

Two naturally occurring plant compounds that are similar in structure to amphetamine

______, the primary active ingredient in khat, an evergreen shrub native to East Africa and the Arabian peninsula



______, coming from the herb Ephedra

vulgaris. Chinese physicians have used ephedra (known to them as mahuang) for more than 5000 years as a herbal remedy.  Ephedrine reduces

appetite, and it also provides a subjective feeling of heightened energy. For these reasons, a number of companies began to market ephedra-containing dietary supplements as weight loss products sold in health food stores.

vHowever, MDMA, MDE, and MDA, called _____, mainly affect _____.

which is more potent with its effects on the central nervous system, amphetamine or methamphetamine ?

The elimination half-life of AMPH ranges from ___ to more than ___ hours depending on the ___ of the ____;

Amphetamine is used to treat ____ and ____

DAT sites were labeled with the radiolabeled cocaine analog ______.

New compounds are substitutes for AMPH: ______, a recently used cathinone derivative, exhibits most of the neurochemical and behavioral profiles of other amphetamine-like stimulants. It may also have the potential for neurotoxicity.

acute effects of MDMA

Chronic effects of MDMA

Nicotine is metabolized in the liver by ______. A major (70-80%) metabolite is _____.

One cigarette contains between ____ mg of nicotine, although no more than ____ mg (____%) actually reaches the bloodstream of the smoker.

How many seconds does it take for nicotine to enter the brain?

where does concentration of nicotine rise the fastest and reach its peak the fastest arteries or veins?

what is the elimination half-life of nicotine?

nicotinic cholinergic receptors are _____ receptors comprising ____ separate protein subunits with only α- and β- (two ____ or ____ and three _____ ) and with two binding sites in the CNS/PNS.

High doses of nicotine lead to a persistent activation of nicotinic receptors and a continuous depolarization of the postsynaptic cell.

This is called

high dose of nicotine exerts a _____ effect that begins with stimulation of nicotinic cholinergic functions but then turns to a nicotinic receptor blockade.

accounts for the features of nicotine poisoning

The drug _____ blocks nicotinic receptors containing α4, α3, or α2 subunits, along with β2 or β4 subunits – _____ α and ____ β composition.

The drug ______ blocks α7-containing nicotinic receptors – ____ α7 composition.

administration of an α7 partial agonist _____ to mice led to improved performance in the novel object recognition test of memory.

Prior intravenous (lV) infusion of the selective nicotinic receptor antagonist  ______ completely blocked the effects of TS on dopaminergic neuron firing.

when nicotinic receptors on the ventral tegmental area are activated it causes release of dopamine in the _______

What happens when genetic deletion of specific nicotinic receptor subunits expressed in the dopaminergic neurons in VTA?

Nicotinic receptors on the VTA contain ___ and ____ subunits and play a particularly important role in the addictive properties of nicotine.

nicotinic receptor activation on parasympathetic and sympathetic nervous system

cigarette smokers weigh an average of _____ less than age-gender matched non smokers due to _____ and _____

Nicotinic receptors in many parts of the brain like VTA play a significant role in nicotine abstinence syndrome after withdrawal. Chronic exposure leads to a compensatory ______ of nicotinic receptors (due to desensitization after repeated exposure).

Surveys indicate that _____% of current smokers in the US would like to quit smoking, and about _____% of daily smokers actually attempt to quit each year. However, the success rate is very low due to addiction to nicotine is so powerful

Behavioral interventions:

Strategies are directed toward discouraging young people from beginning tobacco use or giving it up if it is already habitually used:

Anti-smoking appeals

o Mandated health warnings on cigarette packages by the Surgeon General;

o Levying of high taxes on tobacco products;

o Various self-help programs involving books or manuals are used by smokers;

o Individual or group counseling programs provided by health professionals, particularly those that provide social support and/or coping-skills training to their clients.

Nicotine replacement was first accomplished by formulating a special nicotine-containing chewing gum (nicotine polacrilex).

This has the advantage that nicotine can be absorbed by the buccal mucosa (mucous membranes lining the mouth) rather than the gastrointestinal tract, so the ________

______, an unusual antidepressant medication thought to act by ______ and ______, is reported to REDUCE cravings and were able to QUIT smoking without additional therapeutic intervention.

_______ acts as a partial agonist at high-affinity _____ nicotinic receptors that are expressed in the _____, as well as in other brain areas.



vThis partial agonism elicits a moderate amount of receptor activation, in contrast to the full receptor agonism produced by cigarette-derived nicotine. The resulting effect is a reduction of nicotine cravings and of adverse withdrawal reactions in the abstinent smoker.

Tea leaves contain significant amounts of both caffeine and a related compound called _______ (difference in methyl and hydrogen groups);

Caffeine is normally consumed orally through the beverages in which it is present. Under this condition, it is virtually completely absorbed from the ______. Caffeine absorption begins in the stomach but takes place mainly within the _____.

The plasma half-life of caffeine varies substantially from one person to another, but the average value is about _____ hours

The greatest health risk: ______ is caused due to chronic ingestion of excessive amounts of caffeine, which is characterized by restlessness, nervousness, insomnia, and physiological disturbances including tachycardia (increased heart rate) and gastrointestinal upset.

the most important clinical use of caffeine is ______

Caffeine produces its effects pharmacologically by 3 ways

when adenosine binds to its receptor ____

The United Nation estimated that in 2004 about ____% of the world's adult population (162 million people) use cannabis annually, and about ____% (22.5 million) use it on a daily basis

Chemically, ______ is major active ingredient to produce the psychoactive properties of marijuana

Another cannabis derivative. 

______ generally refers to a relatively pure resin preparation with a very high cannabinoid content.

A typical hand-rolled marijuana cigarette (“joint") consists of around 0.5 - 1 g of cannabis. If cannabis contains 4% of THC, then a 1-g joint contains ____ mg of active ingredient (THC) that is available to the smoker

Burning of the marijuana causes the THC to vaporize and to enter the smoker's lungs in small particles. Only about _____% of the original THC content is absorbed in the lungs.

The reduced bioavailability of THC following oral consumption compared to smoking probably results from both ____ and ____

End products: THC is converted in to several metabolites, notably ____ and ____.

Even though THC levels in the bloodstream decline fairly rapidly after one smokes marijuana, complete elimination from the body is much slower due to persistence of the drug in fat tissue (depot binding). Consequently, the elimination rate, or half-life (T1/2), of THC is generally estimated at around _____ hours.

Both CB1 and CB2 receptors are metabotropic or ionotropic?

what are the 4 cellular effects of cannabinoid receptor activation ?

Synthetic agonists: _____ and _____ are full agonists at both CB1 and CB2 receptors

The first selective CB1 antagonist

Summary of THC effects by CB receptors: Animal studies show that administration of THC to mice leads to a classical "tetrad" (four) of effects consisting of

_______ are responsible for memory impairment in the radial arm maze produced by cannabinoid agonist administration

In 1992, a research group announced that they had isolated a substance with cannabinoid-like activity from the pig brain

Chemical analysis revealed the substance to be a lipid with a structure similar to that of arachidonic acid found in membrane phospholipids. The formal chemical name of this substance is arachidonoyl ethanolamide (AEA), but the researchers gave it the additional name ______

______ is a arachidonic derivative that binds to and activates CB1 receptors

It is synthesized by _______

It is broken down by ______

endocannabinoids (Endo CBs) are generated from ______, a fatty acid commonly found in ______.

why do researchers believe that endo CBs are made and released when needed, no vesicles exist for this substance?

what mechanism triggers endocannibinoid release?

Once inside the cell, endo CBs are metabolized by several enzymes, the best known of which is ________.

cannabinoid receptors are localized _____

endocannabinoids are released ______

Pyramidal neuron release endocannibinoids (influx of Ca2+ cause this) that bind to the CB1 receptor on GABA interneuron and that causes closing of Ca2+ channels through G-protein mechanism and less GABA will be released and therefore less GABA will bind to the pyramidal neuron that normally slows pyramidal cell firing of endocannabinoids

CB1 agonist ____ food consumption and CB1 antagonist ____ food consumption

The wild-type mice showed normal extinction of their fear response (shown by a reduced percent of time spent freezing) over days (decreased freezing response to tone gradually), whereas the mice lacking CB1 receptors continued to exhibit the same fear response.



These and other findings (not shown) suggest that endocannabinoids released during extinction and acting on CB1 receptors in the basolateral amygdala alter synaptic plasticity in a manner that enables the animals to learn that the tone is no longer dangerous. Thus, the endocannabinoid system is involved in the alleviation of fear, thereby functioning to prevent fear responses from becoming too pervasive.

matching - high, buzz, stoned

(euphoria , exhilaration,  disinhibition,  increased laughter)

lightheaded or even slightly dizzy. Tingling (paresthesia, an abnormal skin feeling) sensations in the extremities

calm, relaxed, perhaps even in a dreamlike state

Systemic administration of the general opioid receptor antagonist naltrexone _____ THC self-administration in squirrel monkeys

More specifically, the conditioned place preference produced by a low dose of THC was abolished in _____ receptor knockout mice, whereas the conditioned place aversion produced by a higher THC dose was abolished in mutant mice lacking _____ receptors

The percentage of responders who were current users of at least one illicit drug (typically marijuana) was ____% at 18 to 20 years of age, 11.1% at 30 to 34 years of age, and only 1.0% at 65 years or older.

What and why differences between chronic users and non-users when challenged with a CB1 antagonist?

Oral (not iv or smoke) THC treatment (a combination of THC with the α-adrenergic agonist ______ should be regarded as a replacement therapy) suppresses cannabis withdrawal symptoms.

_____ and ____ from tar through smoking are actually carcinogens;

Anticipatory worry (not fear) is one of the behavioral responses to anxiety stimuli may be initiated by a brain area referred to as the "extended amygdala” like the ______.

CRF may also mediate anxiety-like responses in the LC: CRF containing neurons originating in the central nucleus of the AMY project their CRF-containing axonal terminals to the LC to mediate the hyper-vigilance response by adrenergic mechanism.
This could be mimicked by intracranial injection of CRF that increases firing rate of NE neurons in the LC and increases NE turnover in the amygdala and hypothalamus. b. Infusion of CRF directly into the LC produces anxiety, indicating NE neurons in the LC are activated during stress, which would in turn influence amygdala’s activity to coordinate the vigilance response.

α2-autoreceptor antagonist ______ (increases NE release) can mimic a wide range of alerting and fear responses

Clinically, this memory mediated by catecholamines has been implied by clinical trials in which the β-adrenergic antagonist _______ effectively reduced some of the symptoms of PTSD

Norepinephrine cells in the locus coruleus are excited by ______

Norepinephrine cells in the locus coruleus are inhibited by ____, ____, and ____

these 4 enhance GABA function by binding to other sites on the GABAa receptor and causing sedation, reduced anxiety, and anticonvulsant effects