Psychopharmacology psychopharmacology – study of drugs and behavior Drugs and behavior – PSY 459 some general concepts and issues psychoactive drugs – change the way you feel

Why do people take psychoactive (particularly illicit) drugs? To feel good (positive reinforcement – likely cause DA release!) psychological dependence **greatest amount of psychological dependence occurs if the rewarding effects of drugs happen very quickly after behaviors associated with them.

drug rewards that happen very soon after a behavior – strong positive reinforcement for that behavior ex. prep for heroin injection, crack smoking, etc.

Why do people take drugs? 2. To avoid feeling bad (reduce withdrawal) (negative reinforcement) chemical dependence

Important issues related to how and why we take drugs pharmacokinetics: includes drug absorption, distribution, metabolism and drug excretion absorption – how we take drugs into the body distribution - how the drug reaches its primary site of action metabolism - how our body breaks drugs down excretion - how we eliminate drugs

pharmacokinetics....... how a drug is taken into the body…… for drugs of abuse - the more rapidly the drug gets to the brain – the greater the abuse liability!

routes of administration oral injection subcutaneous intramuscular intravenous - reaches brain in ~ 10 secs quick response but also most dangerous inhalation - reaches brain in ~8 secs dermal – absorbed through the skin buccal or nasal membranes

pharmacokinetics....... 2. absorption – all drugs that change how we feel must be able to cross the blood brain barrier 3. pharmacodynamics how does drug produce its effects on behavior (ie what neurotransmitter or neurotransmitters are affected)

ex of pharmacodynamics – 1. cocaine – blocks reuptake of monoamine neurotransmitters (most important DA) 2. nicotine acts as an agonist at nicotinic cholinergic receptors 3. alcohol works on virtually every neurotransmitter

4. metabolism (detoxification or breakdown) how a drug is broken down or made into inactive forms mostly done by the liver – via enzymes!

Tolerance, Dependence, Withdrawal, etc…… tolerance – either decreased effectiveness or potency of a drug

Mechanisms for Tolerance metabolic tolerance – enzyme induction- enzymes – speed up a chemical reaction with repeated exposure, enzymes get better at breaking down drug or liver makes more enzymes

Mechanisms for Tolerance metabolic tolerance – enzyme induction- enzymes are either better at breaking down drug or liver makes more of them implications?

Mechanisms for Tolerance metabolic tolerance – enzyme induction cross tolerance – tolerance to one drug results in tolerance to other drugs (usually that need similar enzymes for breakdown) Implications:

Mechanisms for Tolerance cross tolerance – tolerance to one drug results in tolerance to other drugs (usually that need similar enzymes for breakdown) Implications: Person shows up unconscious at ER and is an alcoholic – given a barbiturate for surgery;

What if amount of drug reaching brain/body is unchanged? tolerance can still occur when the amount of drug reaching the brain/body is unchanged pharmacodynamic or physiological tolerance –

What if amount of drug reaching brain/body is unchanged? pharmacodynamic or physiological tolerance – “for every action, there is an equal and opposite reaction (in your brain)”

Ways that the brain may try and compensate…… Use alcohol as an example – Acutely – alcohol decreases glutamate activity and increases GABA activity Chronic alcohol -------- brain’s compensatory response?

How might the brain try and compensate for this change if it is chronic? upregulation of GLU receptors – increase the number or sensitivity of glutamate receptors to compensate for decreased activity and try to get activity back to normal levels….

How might the brain try and compensate for this change if it is chronic? upregulation of GLU receptors – increase the number or sensitivity of glutamate receptors to compensate for decreased activity and try to get activity back to normal levels…. what happens during alcohol withdrawal? now have too many (or too sensitive) glutamate receptors – overexcitation, seizures, etc.

How might the brain try and compensate for this change if it is chronic? down regulation of GABA receptors – to compensate for increased activity and try to get activity back to normal levels…. – reduce n or sensitivity of GABA receptors

How might the brain try and compensate for this change if it is chronic? down regulation of GABA receptors – to compensate for increased activity and try to get activity back to normal levels…. – reduce n or sensitivity of GABA receptors what happens during alcohol withdrawal?

Explanation for various withdrawal symptoms the exposure of compensatory changes in brain (and body perhaps) likely explain a number of withdrawal symptoms (that are often opposite of the effects that the drug causes)

chemical see-saw drug brain response

chemical see-saw heroin constipation

heroin WD diarrhea

Environmental Tolerance Drugs taken in the same environment can also display tolerance associated with the conditioned cues ex. heroin explanation – compensatory changes in brain in EXPECTATION of drug

5. excretion (elimination) how a drug once broken down (or not) is eliminated from body most psychoactive drugs metabolites excreted in urine