Edit · Neuropharmacology: Glutamate, GABA, Drugs, Opioids & Anxiety BEST

Q1. Which enzyme is involved in the conversion of glutamine to glutamate?

Glutaminase — converts glutamine into glutamate inside the presynaptic neuron.

Q2. Which of the following statements is NOT true regarding the vesicular glutamate transporter protein?

NOT true: that VGLUT (vesicular glutamate transporter) reuptakes glutamate from the synapse. VGLUT only packages glutamate into vesicles; there are 3 isoforms (VGLUT1-3).

Q3. Glutamate is inactivated by what?

Glial (astrocyte) uptake via EAATs (excitatory amino acid transporters) — not direct presynaptic neuronal reuptake.

Q4. How do astrocytes contribute to the regulation of glutamate levels?

They take up glutamate via EAATs (excitatory amino acid transporters) and convert it to glutamine (via glutamine synthetase), then shuttle it back to neurons — the glutamate-glutamine cycle.

Q5. AMPA and kainate receptors are what?

Fast, ionotropic (ligand-gated cation channel) glutamate receptors that mediate fast excitatory transmission. (AMPA = α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid)

Q6. Which of the following is NOT true regarding the NMDA (N-methyl-D-aspartate) receptor?

NOT true: that NMDA is voltage-independent, not Ca2+ permeable, or needs no co-agonist. (It IS blocked by Mg2+, requires glycine co-agonist, and is highly Ca2+-permeable.)

Q7. NMDA (N-methyl-D-aspartate) receptors can be blocked competitively by ______ and non-competitively by ______.

Competitive: AP5/APV (2-amino-5-phosphonovaleric acid, at the glutamate site). Non-competitive: PCP (phencyclidine), ketamine, MK-801 (dizocilpine), Mg2+ (block the open channel pore).

Q8. The opening of the channel associated with the NMDA (N-methyl-D-aspartate) receptor is unique because it requires both ______ and ______.

Glutamate (+ glycine co-agonist) binding AND postsynaptic depolarization (to relieve the Mg2+ block).

Q9. What enzyme is involved in the synthesis of GABA?

GAD (glutamic acid decarboxylase) — requires vitamin B6 as a cofactor. (GABA = gamma-aminobutyric acid)

Q10. Which of the following is NOT involved in the recycling of GABA after it has been released into the synapse?

NOT involved: glutamate-system transporters (EAATs = excitatory amino acid transporters, VGLUT = vesicular glutamate transporter). GABA's own recycling uses GAT-1/2/3 (GABA transporters) reuptake plus GABA-T (GABA transaminase) breakdown.

Q11. The enzyme that breaks down GABA is what?

GABA-T (GABA transaminase) — breaks GABA (gamma-aminobutyric acid) into succinic semialdehyde, feeding the Krebs cycle.

Q12. The GABA-A (gamma-aminobutyric acid type A) receptor complex has binding sites for all BUT which of the following?

NOT a site: glutamate (or other unrelated transmitters). Real sites = GABA, benzodiazepine, barbiturate, neurosteroid, picrotoxin/channel.

Q13. The GABA-A (gamma-aminobutyric acid type A) receptor can be blocked competitively by ______ and non-competitively by ______.

Competitive: bicuculline (GABA site). Non-competitive: picrotoxin (channel pore).

Q14. Which of the following drugs is an agonist at the GABA-A (gamma-aminobutyric acid type A) receptor?

Muscimol — direct agonist at the GABA orthosteric site.

Q15. Which drug is an agonist at the GABA-B (gamma-aminobutyric acid type B) receptor?

Baclofen.

Q16. Benzodiazepines act how?

Positive allosteric modulators at GABA-A (gamma-aminobutyric acid type A) receptors (α/γ site) — increase the FREQUENCY of Cl- channel opening; only work when GABA is present.

Q17. An inverse agonist acts how?

Binds the same site as the agonist but produces the opposite effect (e.g., DBI (diazepam binding inhibitor) and beta-carbolines decrease GABA-stimulated Cl- flux — anxiogenic).

Q18. Which of the following explains the rapid absorption of cocaine?

Route of administration (smoking/IV = large absorptive surface, fast entry) plus cocaine's high lipid solubility (crosses the BBB, blood-brain barrier, quickly).

Q19. Which of the following statements about the mechanism of action of cocaine is NOT true?

NOT true: that cocaine causes monoamine RELEASE (that's amphetamine). Cocaine only BLOCKS reuptake at DAT (dopamine transporter), NET (norepinephrine transporter), and SERT (serotonin transporter).

Q20. The fact that rats can learn to respond on a particular schedule of reinforcement, depending on whether they were injected with cocaine or saline, demonstrates what about cocaine?

Drug discrimination — cocaine produces a distinct, reliably detectable interoceptive (subjective) state.

Q21. Microinjection experiments suggest that psychostimulant-induced locomotion is mediated by ______, whereas stereotypy is mediated by ______.

Locomotion: nucleus accumbens (mesolimbic terminal). Stereotypy: dorsal striatum/caudate-putamen (nigrostriatal terminal).

Q22. What do we know about dopamine transporter (DAT) knockout mice?

They still show some residual cocaine reward/self-administration (reduced, not eliminated) — implicates SERT (serotonin transporter) as a secondary route.

Q23. And what do we know about knock-in mice with cocaine-insensitive DATs (dopamine transporters)?

They show NO cocaine-induced locomotion or reward — proof cocaine must physically bind DAT to produce its effects.

Q24. PET (positron emission tomography) studies demonstrate that the high following cocaine in humans is associated with all BUT which of the following?

NOT associated: duration of DAT (dopamine transporter) blockade. The high tracks with the SPEED/degree of striatal DAT occupancy, not how long it lasts.

Q25. According to Post, tolerance is favored by ______, while sensitization is favored by ______.

Tolerance: continuous/frequent dosing. Sensitization: intermittent, spaced-out dosing.

Q26. Sensitization of locomotion can be initiated by chronically infusing amphetamine or cocaine directly into where?

VTA (ventral tegmental area) — the initiation site.

Q27. The expression of sensitization of locomotion to amphetamine and cocaine is associated with increased dopamine release where?

Nucleus accumbens — the expression/output site.

Q28. Which of the following statements about the mechanism of amphetamine is NOT true?

NOT true: that amphetamine is only a reuptake blocker. It causes active RELEASE by reversing DAT (dopamine transporter)/NET (norepinephrine transporter)/SERT (serotonin transporter), plus MAO (monoamine oxidase) inhibition and VMAT2 (vesicular monoamine transporter 2) disruption.

Q29. At low to moderate doses, opiates produce all BUT which of the following?

NOT produced: pupil dilation or CNS (central nervous system) stimulation. Opiates cause miosis (constriction), sedation, analgesia, and decreased GI (gastrointestinal) motility.

Q30. Which of the following statements is NOT true about heroin?

NOT true: that heroin is less lipid soluble than morphine, or acts directly without conversion. Heroin is a prodrug, MORE lipid soluble than morphine, converted to morphine via 6-MAM (6-monoacetylmorphine) in the brain.

Q31. Which of the following statements is NOT true regarding partial opiate agonism?

NOT true: that partial agonists have no ceiling effect or match full-agonist max effect. They DO have a ceiling effect and CAN precipitate withdrawal in a full-agonist-dependent patient.

Q32. Buprenorphine is an opiate ______. (How does buprenorphine work?)

Partial agonist (at the mu, MOR (mu-opioid receptor), receptor).

Q33. Naltrexone is an opiate ______. (How does naltrexone work?)

Antagonist (long-acting, mainly at the mu, MOR (mu-opioid receptor), receptor).

Q34. Pentazocine is an opiate ______. (What is its mechanism?)

Mixed agonist-antagonist (kappa, KOR (kappa-opioid receptor), agonist / mu, MOR (mu-opioid receptor), antagonist-or-partial-agonist).

Q35. What are the four endogenous opiate ligands?

Endorphins, enkephalins, dynorphins, and endomorphins.

Q36. Morphine, enkephalins, and dynorphin act at which kind of receptors?

Metabotropic (G-protein coupled, Gi-linked) opioid receptors.

Q37. Which of the following is NOT true regarding opiate peptides?

NOT true: any mismatched pairing (e.g., dynorphin→mu) or that opioid peptides act at ionotropic receptors. Correct: endorphins→mu (MOR), enkephalins→delta (DOR, delta-opioid receptor), dynorphins→kappa (KOR), all metabotropic.

Q38. Which of the following statements about opiates and reinforcement is NOT true?

NOT true: that opiates directly excite VTA (ventral tegmental area) dopamine neurons. Real mechanism = disinhibition (mu receptors inhibit GABA, gamma-aminobutyric acid, interneurons that normally inhibit DA, dopamine, neurons).

Q39. What area of the brain coordinates the various components of fear and other emotions?

The amygdala, especially the central nucleus.

Q40. The ______ appears to play an important role in initiating sustained emotional responses of anxiety when danger signals are unclear.

BNST (bed nucleus of the stria terminalis).

Q41. Which of the following sequences precedes the release of cortisol in response to stress?

PVN (paraventricular nucleus of the hypothalamus) releases CRF (corticotropin-releasing factor) → anterior pituitary releases ACTH (adrenocorticotropic hormone) → adrenal cortex releases cortisol.

Q42. Which of the following is NOT true regarding CRF (corticotropin-releasing factor) acting as a neurotransmitter?

NOT true: that CRF's neurotransmitter action in the amygdala is anxiolytic, or limited to triggering the HPA (hypothalamic-pituitary-adrenal) axis. CRF is actually ANXIOGENIC as a neurotransmitter and acts independently of the HPA axis too.

Q43. Anxiolytic drugs include all BUT which of the following?

NOT an anxiolytic class: antipsychotics (D2, dopamine type 2 receptor, antagonists). Real classes: barbiturates, propanediols, benzodiazepines (BZs), buspirone (+ some antidepressants).

Q44. Differences in the onset and duration of action of barbiturates are correlated with differences in their what?

Lipid solubility.

Q45. What do we know about the duration of action of benzodiazepines?

Depends on biotransformation — long-acting BZs (benzodiazepines) form active metabolites (prolonging effect); short-acting BZs conjugate directly to inactive metabolites (shorter effect).

Q46. Benzodiazepines increase chloride (Cl-) conductance how?

By increasing the FREQUENCY of GABA-A (gamma-aminobutyric acid type A) Cl- channel opening (positive allosteric modulation; only works when GABA is present).

Q47. Flumazenil acts how?

As a neutral, competitive benzodiazepine (BZ) receptor antagonist — no effect alone; blocks both BZ agonists and inverse agonists, but not GABA (gamma-aminobutyric acid) itself.

Q48. Diazepam binding inhibitor and beta-carbolines are what?

Inverse agonists at the benzodiazepine (BZ) receptor — anxiogenic (decrease GABA-stimulated Cl- flux). (DBI = diazepam binding inhibitor; GABA = gamma-aminobutyric acid)

Q49. In a conflict paradigm, what effect do anxiolytics have?

They INCREASE punished responding during the conflict (anticonflict effect) — reduce the suppressive effect of shock-paired punishment.

Q50. The role of the locus coeruleus in anxiety is supported by all BUT which of the following?

NOT supported: that anxiolytics increase LC (locus coeruleus) firing, or that LC activity decreases to threat. True: anxiolytics (BZs = benzodiazepines, SSRIs = selective serotonin reuptake inhibitors, TCAs = tricyclic antidepressants, MAOIs = monoamine oxidase inhibitors) INHIBIT LC firing; novelty/threat INCREASES it.