Psychopharmacology

Psychopharmacology Study of the effect of drugs on the nervous system and on behavior

Some Terminologies Drug Effects - changes a drug produces in an organism’s physiological processes and behavior Sites of Action - location at which molecules of drugs interact with molecules located on or in cells of the body Pharmacokinetics - “movement of drugs”, process by which drugs are absorbed, distributed within the body, metabolized and excreted

Routes of Administration: Intravenous Injection (IV) - Fastest route; entire dose reaches the bloodstream at once Intraperitoneal Injection (IP) - peritoneal cavity ; space that surrounds the stomach, intestines, live and other abdominal organs Intramuscular Injection (IM) Subcutaneous Injection (SC) - space beneath the skin Oral administration

Routes of Administration: Sublingual Administration - substance by placing it beneath the tongue Intrarectal Administration - substance into the rectum Inhalation Topical Administration - substance directly onto the skin or muscle membrane

Routes of Administration: Intracerebral Administration - To study the effects of a drug in specific region of the brain, a researcher will inject a very small amount of a drug directly into the brain Intracerebroventricular (ICV) Administration - Drug is injected into a cerebral ventricle

Distribution of Drugs Within the Body Sites of action - located on or in particular cells in the central nervous system One of the factors determining the rate at which the drug that is present in the bloodstream reaches sites of action within the brain is lipid solubility All are eventually excreted – primarily by the kidneys Enzymatic deactiviation Occasionally, the transformed molecule is even more active than the one that is administered

Reasons Why Drugs Vary in their Effectiveness Different drugs may have different sites of action Affinity for the molecules to which they can attach - readiness with which the two molecules join together High affinity will produce effects at a relatively low concentration Low affinity must be administered in relatively high doses

Effects of Repeated Administration Tolerance Sensitization Withdrawal Symptoms

Sequence of Synaptic Activity Neurotransmitters are synthesized and stored in synaptic vesicles Synaptic vesicles travel to the presynaptic membrane When an axon fires, the neurotransmitters are released into the synaptic cleft

Sequence of Synaptic Activity Molecules of the neurotransmitters bind with the postsynaptic receptor, causing receiving neurons’ particular ion channels to open, which produces excitatory or inhibitory postsynaptic potentials The effects of the neurotransmitters are relatively brief by their reuptake by transporter molecule in the presynaptic membrane or by their destruction by enzymes Monoamine Oxidase (MAO)

Sites of Drug Action Types of drugs that affects synaptic transmission: Antagonist – Those that block or inhibit the postsynaptic effects. Receptor Blocker (Direct Antagonist) – A drug that binds with a receptor but does not activates it; prevents the natural ligand from binding with a receptor

Sites of Drug Action Types of drugs that affects synaptic transmission: Agonist – Those that facilitate the effects of a particular neurotransmitter on the postsynaptic cell. Direct Agonist – Drug that binds and activates a receptor.

Effects of Agonists Drug serves as a precursor Drug stimulates release of neurotransmitters (NT) Drug stimulates postsynaptic receptors (direct agonist) Drug blocks autoreceptors; increase synthesis/release of NT Drug blocks reuptake Drug inactivates enzymes that breakdown NT

Effects of Antagonist Drug inactivates synthetic enzymes; inhibits synthesis of NT Drug prevents storage of NT Drug Inhibits release of NT Drug blocks postsynaptic receptor (direct antagonist) Drug stimulates autoreceptors; inhibits synthesis/release of NT

Neurotransmitters Most synaptic communication is done by the two neurotransmitters: Glutamate - excitatory effects Gamma-aminobutyric acid (GABA) - inhibitory effects Glycine - another inhibitory neurotransmitter found in the spinal cord and lower brain stem Other neurotransmitters, have modulatsing effects Amino acids

Other Neurotransmitters Acetylcholine Monoamine (catecholamines) Epinephrine Norepinephrine Dopamine Monoamine (Indolamine) Serotonin

Acetylcholine (ACh) 2 components Afferent axons of the CNS Choline – A substance derived from the breakdown of lipids Acetate – The anion found in vinegar; also called acetic acid Afferent axons of the CNS mostly excitatory muscle movement

Acetylcholine (ACh) Systems of Acetylcholinergic Neurons: Dorsolateral Pons – Responsible for triggering most of the characteristics of REM sleep Basal Forebrain – Involved in activating the cerebral cortex and facilitating learning, especially perceptual learning Medial Septum (part of the limbic system) – Control the electrical rhythms of the hippocampus and modulate its functions which include the formation of particular kinds of memories

Dopamine (DA) Excitatory and inhibitory postsynaptic potentials Movement, attention, learning and the reinforcing effect of drugs Precursors of Dopamine Tyrosine – Precursor for the two major catecholamine neurotransmitters (DA and norepinephrine); enzyme convert it to L-DOPA L-DOPA – Biologically active form of DOPA; precursor of catecholamines; enzyme covert it to Dopamine

Dopamine (DA) Systems of Dopaminergic Neuron Nigrostriatal system – located in the substantia nigra and project their axon to the neostriatum; an important part of the basal ganglia, involved in the control of movement. Patkinson’s Disease Mesolimbic system – Located in the ventral tegmental area and projects their axons to several parts to the limbic system, including the nucleus accumbens, amygdala and hypothalamus. The nucleus accumbens play an important role in the reinforcing effects of certain categories of stimuli, including those of drugs people abuse.

Dopamine (DA) Systems of Dopaminergic Neuron Mesocortical system – Their axons project to the prefrontal cortex. These neurons have an excitatory effect on the frontal cortext and thus affect such functions as formation of short-term memories, planning, and strategy preparation.

Norepinephrine/Noradrenaline (NE) Causes an increase in vigilance – attentiveness to events in the environment System of Noradrenalinergic Neurons Locus Ceoruleus – Located in the pons;

Serotonin (5-TH) Regulation of mood Control of eating, sleep and arousal Regulation of pain Controlling dreams Suppresses certain categories of behaviors and reduces the likelihood that an animal acts impulsively.

Serotonin (5-TH) System of Serotonergic Neurons Raphe Nuclie – Found at or near the midline of the brain stem.