Psychopharmacology Exam 2

Pharmacodynamic tolerance

Related to drug effects on neurotransmitters and their functioning. has multiple mechanisms, one of which is depletion of neurotransmitters. This happens when a drug causes an excessive release of a neurotransmitter, before it can replenish, which decreases its effects and leads to higher intakes. A drug can also affect the synthesis of the neurotransmitter directly, so increased amounts of a drug actually leads to decreased effects, because there are so few neurotransmitters available. More or both drugs will be needed to achieve the previous effects.

Describe the behavioral and psychostimulant effects of the amphetamines, being sure to include how these effects vary with increasing dosage and the type of behavior (purposeful and purposeless).

-Amphetamines are a class of drugs that are approved to treat conditions such as narcolepsy, attention deficit hyperactivity disorder (ADHD), and in the past were approved for mood elevation and appetite suppression. These drugs in low and moderate doses can facilitate performance in tasks that require continuous attention and physical tasks that require quickness or also strength -in higher doses performances are usually diminished. Impairments are usually seen in tasks that require fluidity and accuracy in higher doses of amphetamines. With the use of amphetamines there are behaviors exhibited called purposeless behaviors. Purposeless behaviors increase with amphetamine use. In animal studies, the behaviors exhibited are much like the behaviors exhibited in humans with OCD (obsessive compulsive behaviors). These examples are considered to be induced by stress as well as stress-inducing. For example, grooming, swaying, gnawing, licking. In humans these behaviors are referred to as punding. Can be things like teeth grinding, nail biting, skin picking, tapping or leg shaking, and fidgeting in general. -This is caused by increased dopamine in the movement producing center of the brain called the basal ganglia -The rate of high frequency behaviors are decreased which is why amphetamines are prescribed to patients with ADHD. Attentiveness is increased as disruptive behaviors are decreased- which before, with a diagnosis of ADHD, would be the opposite. Rates of low-frequency behaviors are known to increase with the use of amphetamines.

Amphetamines have several pharmacodynamic effects on monoamine neurotransmitters, particularly dopamine. Describe the effects that amphetamines have, including an example of how different amphetamines differ in their mechanisms of action. Also describe the aversive effects to the CNS that can result from chronic amphetamine use

-The short term amphetamine usage typically results in a decrease of catecholamine receptors. This is attributed to the agonistic effects seen with abstinence syndrome. -Specifically speaking, there is an overall decrease of neurons within the cingulate, limbic, and paralimbic cortices. Additionally smaller hippocampal areas have been seen especially in methamphetamine users leading to memory impairments. -amphetamine usage can cause inhibited MAO activity such as enzymatic oxidization. This leads to lower rates of dopamine breakdown, increasing the overall amount of dopamine present. Causing non-enzymatic oxidation to take place, monoamines are broken down into various toxic compounds triggering the degeneration of axon terminals and terminal buttons. -Chronic usage of methamphetamine and methcathinone has been shown to deplete the amount of dopamine present within the basal ganglia -Mood is also enhanced with amphetamines as they increase alertness, vigor, and more physiological arousal in general -Ecstasy, dioxymethamphetamine/MDMA primarily increases the release of catecholamines, less effect on blocking reuptake. It also has a greater effect on 5-HT transporters than DA and NE which is why it is classified as a hallucinogen. To some extent MAO's are somewhat blocked by amphetamines. This prevents enzymatic destruction of monoamine neurotransmitters. Dopaminergic activity in the nucleus accumbens is increased by amphetamines and cocaine. They also increased serotonergic activity but the abuse potential is due to the reinforcing effects of increased dopamine

Cocaine can be administered several different ways. First, address the differences in pharmacokinetics of oral, inhaled, and intranasal cocaine administration, then compare/contrast effects of cocaine with those of amphetamine on any four variables related to the themes of this course - behavioral effects, pharmacodynamics/pharmacokinetics, and tolerance/dependence/withdrawal.

The abuse potential of amphetamines and psychostimulants is extremely high, the highest of all drugs. The withdrawal effects of amphetamines are the same for cocaine, lethargy, hunger, exhaustion- essentially the opposite effects of the drug. An abstinence effect can be seen due to the possibility of a short-term decrease in sensitivity of catecholamine receptors. But, the abstinence effect is still less than in sedative-hypnotic drugs. Psychologican dependence is extremely strong with amphetamines due to the enhanced mood and energy being strong reinforcers.

secondary psychological dependence

This is defined by a craving for the drug to alleviate fear or anxiety caused by the withdrawal.

Context-Specific Tolerance: Habituation

a basic form of learning when a stimulus activates receptors leading to a reflexive response. When the stimulus is presented repeatedly and without variation, the response decreases in magnitude until it eventually stops all together. With respects to tolerance and cross tolerance, we can see it develop because the person would need more of the stimulus or a different kind of variation of it in order to keep the response.

Physical, or physiological, dependence

is defined by the presence of abstinence syndrome (physical disturbances develop when administration of a drug is suspended after prolonged use, or with administration of a specific antagonist). It is also called withdrawal. Its effects are generally opposite to the effects of the drug. The length of those symptoms depend on the length of action of the drug. If a drug has a short plasma half-life, the withdrawal period will be shorter too, but with intense symptoms. For drugs with a long plasma half-life, that have been taken for a long period of time, the withdrawal will be prolonged, but with less intense symptoms.

Context-Specific Tolerance: Instrumental Conditioning

is in contrast to classical conditioning where there is an unconditioned stimulus that triggers an unconditioned response. The form and frequency of behavior depends on the consequences of that behavior. Positive and negative reinforcers play a role in this, positive reinforcing stimuli is the presentation of something valued or rewarding after the behavior while negative reinforcing stimuli is the removal of something unpleasant or aversive after a behavior, or something that delays something negative. Drug-taking behavior can be reinforced or punished, which will influence subsequent frequencies of this behavior. The rate of development of tolerance will depend on the difficulty of the task and the availability of compensatory responses.

Primary psychological dependence

refers to a strong compulsion or desire to experience the effects of a drug because it produces pleasure or reduces psychic discomfort a strong compulsion to experience the effects of a drug due to the pleasurable effect or reduction of discomfort. This dependence comes when drug-taking behavior is followed by rewarding/reinforcing effects, typically pleasure (positive reinforcement) or relief from something aversive, such as pain, anxiety, or discomfort (negative reinforcement).

Cross Tolerance

the development of tolerance to one drug results in decreased sensitivity to another drug or type of drug. This can be dangerous because larger amounts of the drug are needed to produce the same effects, which can lead to overdoses. Also, tolerance builds up to the pleasurable effects of the drug, but not necessarily to the side effects, which can be severe.

Pharmacokinetic tolerance

the liver's ability to synthesize more metabolizing enzymes with higher drug doses the drug will be metabolized before any of the effects start appearing, leading to more intake of the drug in order to feel its effects, which only increases one's tolerance. This can result in cross-tolerance because the P450 enzymes in the liver can metabolize different drugs. So if one builds up a tolerance to one drug, they will also develop a tolerance to other drugs that are metabolized by the same enzymes.

Context-Specific Tolerance: Classical Conditioning

when a neutral stimulus (aka conditioned stimulus) comes before an unconditioned stimulus in order to elicit an unconditioned response. As this relationship is solidified, the presentation of the conditioned stimulus signals that something is going to happen. With a Conditioned Response that is different from Unconditioned Response (and usually weaker), it appears that the same dose of a drug produces a weaker response with repeated administrations; so to get the stronger response, the equivalent of the original UCS, more drug is needed - and this is tolerance.