1● an appetitive stimulus given to a human or some other animal
to alter its behavior.
● It's typically serve as reinforcers, which causes the probability
of that behavior's occurrence to increase when presented after
a behavior.
REWARD
2 a collection of brain structures that attempts to regulate and
control behavior by inducing pleasurable effects
THE REWARD SYSTEM
3THE REWARD SYSTEM 3 parts
○ Ventral tegmental area (VTA)
○ Nucleus Accumbens (NAc)
○ Prefrontal cortex
4Many drugs of abuse activate the reward circuitry of the
MFB, which requires a stimulation to activate the
mesocorticolimbic dopamine system.
Mesolimbic pathway
5● It's the major target of the electric stimulation producing
pleasure
NUCLEUS ACCUMBENS (NAc/NAcc)
6• pleasure center of the brain (majority of pleasure is
processed in this area)
Nucleus Accumbens
7 is crucial for the rewarding effects of the psychomotor
stimulants and is important but perhaps not crucial for the
rewarding effects of the opiates (morphine, heroin) nicotine,
cannabis and ethanol.
Dopamine
8 is the primary NT involved in reward pathway
Dopamine
9● Lesions of the nucleus accumbens attenuated the rewarding
effects of cocaine and amphetamine.
● Morphine, amphetamine and cocaine are self-administered
directly into the nucleus accumbens
NUCLEUS ACCUMBENS HYPOTHESIS
10• It just states that there are stages that a person experienced
before reaching the endpoint → Drug Dependence
Jellinek Curve Stages
11− party drugs, liquid ecstasy
− can cause palpitations → high electrical impulse → can cause burns
in the heart
Gamma hydroxy butyrate (GHB)
12– drugs that activates g-protein receptors
• Type II (G-protein coupled receptors) – responsible for
producing secondary messengers
• MOA: inhibits Ventral Tegmental Area → inhibits
release of GABA and promote release of Dopamine →
activation of nucleus accumbens → pleasure →
rewarding effect
CLASS I
13– drugs that mediates their effect by ionotropic
receptors
Type I (Ionotropic receptors) controls the movement of ions
CLASS II
14drugs that affect transporters of biogenic amine (particularly VAT and VMAT)
• inhibits reuptake
• 2 MOA:
o Promote release of dopamine
o Increases binding of glutamate
CLASS III
15 Disinhibition of dopamine (DA) neurons in the ventral
tegmental area (VTA) through drugs that act via Gi0- coupled
receptors
Opiods
16MOA: Mimics endogenous opiates (ex: endorphins,
enkephalins)
Opiods
17– main receptors producing dysphoria
(feeling of uneasy, unhappy, or dissatisfied)
Kappa receptors (κ)
18– main receptors that produce euphoria
Mu receptors (μ)
19activates dopamine neurons and inhibit GABA
Opioid receptors
20 – opioid antagonist (toxicity)
NALOXONE, NALTREXONE
21 – long-acting opioid (tx of addiction)
METHADONE, BUPRENORPHINE
22 – mitigates many of sympathetic signs (ex:tachycardia)
CLONIDINE
23 – clonidine analog with less hypoTN
LOFEXIDINE
24● From Cannabis sativa
● mainly act through presynaptic inhibition
● a powerful psychoactive substance
● Like opioids, THC causes disinhibition of dopamine
neurons, mainly by presynaptic inhibition of GABA neurons
in the VTA.
CANNABINOIDS
25targets GABA B receptors, which are located on both cell types. However, GABA neurons are more sensitive to GHB than are DA neurons, leading to disinhibition at concentrations typically obtained with recreational use.
Gamma-hydroxybutyric acid (GHB)
26● First synthesized in 1960 and introduced as a general
anesthetic
● “club drug”
● “liquid ecstasy,” “grievous bodily harm,” or “date rape drug.”
Gamma-hydroxybutyric acid (GHB)
27is a weak agonist, only GABA neurons are inhibited at the
concentrations typically obtained with recreational use.
Gamma-hydroxybutyric acid (GHB)
28MOA: activates G coupled receptors but target GABA B
receptors
Gamma-hydroxybutyric acid (GHB)
29 (found in spinal cord) – target of GHB
GABA B
30 (found in brain) – target of BZDs, Barbiturates,
anxiolytic drugs
GABA A