Neuro Box 7

It is now widely recognized that drugs of abuse usurp control over the neural circuitry that mediates ———-, producing ———- that leads to ——-

learning about natural rewards, (producing) an artificial high that tricks the brain into following a path , (to) maladaptive consequences

psychopharmacology=

the study of how drugs impact the nervous system to influence psychological/behavioral states

(Drugs can influence synaptic communication at multiple sites)

• an ——- can substitute for the endogenous (internally manufactured) drug, binding to the receptor on the postsynaptic cell and producing a similar cellular effect

AGONIST

(Drugs can influence synaptic communication at multiple sites)

• For example, an agonist can substitute for the endogenous (internally manufactured) drug, binding to the receptor on the —— and producing a———

postsynaptic cell ; (a) similar cellular effect

(Drugs can influence synaptic communication at multiple sites)

• drug —— bind to the receptor, but do not engage the same cellular consequences. Instead, the antagonist acts as a kind of roadblock that effectively prevents an agonist from having its usual effect on the postsynaptic cell

ANTAGONISTS

(Drugs can influence synaptic communication at multiple sites)

• drug antagonists bind to the receptor, but do not engage the same cellular consequences. Instead, the antagonist acts as a kind of —- that ——-

roadblock (that) effectively prevents an agonist from having its usual effect on the postsynaptic cell

(Drugs can influence synaptic communication at multiple sites)

• Drugs can also influence function in a less direct manner.

  • For example, some drugs increase neurotransmitter availability by ———- or by ———- into the presynaptic neuron.

enhancing release ;(or by) blocking their reabsorption (reuptake)

In general, drugs of abuse impact the nervous system by —-

promoting the release of a particular neurotransmitter or by emulating its action

psychostimulants influence the neurotransmitter —-

dopamine (DA)

psychostimulants influence the neurotransmitter dopamine (DA) by:

• blocking its reuptake (cocaine)

or

• promoting its release (amphetamine)

psychostimulants influence the neurotransmitter dopamine (DA) by:

• blocking its reuptake (—?——)

(cocaine)

psychostimulants influence the neurotransmitter dopamine (DA) by:

• blocking its reuptake (cocaine)

or

• — ———-

promoting its release (amphetamine)

psychostimulants influence the neurotransmitter dopamine (DA) by:

• blocking its reuptake (cocaine)

or

• promoting its release (————-)

(amphetamine)

psychostimulants examples:

- cocaine & amphetamine

Opiates, such as morphine and heroin, have their effect by ——

emulating endogenous opioids (endorphins) that engage the mu opioid receptor

Opiates, such as morphine and heroin, have their effect by emulating ———- that engage the mu opioid receptor

endogenous opioids (endorphins)

Opiates, such as morphine and heroin, have their effect by emulating endogenous opioids (endorphins) that engage the ——- receptor

mu opioid

Another common addictive substance, nicotine, engages ——- receptors

acetylcholine

sedatives (alcohol, valium) act, in part, through their impact on —-neurons

GABAergic

Drugs of abuse appear to promote addiction by influencing neurons within particular brain regions, such as the nucleus accumbens

• Many of the neurons within this region have ——- that allow for multiple synaptic contacts

spiny dendritic fields

Drugs of abuse appear to promote addiction by influencing neurons within particular brain regions, such as the nucleus accumbens

• Many of the neurons within this region have spiny dendritic fields that allow for multiple synaptic contacts

  • These ———- receive input from neurons that release an endogenous opioid that engages the mu receptor

medium spiny neurons

In addition, dopaminergic neurons project from a region of the midbrain (the ———)

(the) ventral tegmental area (VTA)

In addition, dopaminergic neurons project from a region of the midbrain (the ventral tegmental area [VTA]) and ——-

innervate the spiny neurons as they pass through en route to other regions (e.g., the prefrontal cortex)

Other psychoactive drugs influence the activity of neurons within the nucleus accumbens (NA) by:

• modulating opioid/dopamine release

• engaging receptors on the medium spiny neurons

• or by influencing the inhibitory action of GABAergic neurons that regulate neural activity

Other psychoactive drugs influence the activity of neurons within the nucleus accumbens (NA) by:

• modulating ———release

• opioid/dopamine release

Other psychoactive drugs influence the activity of neurons within the nucleus accumbens (NA) by:

• modulating opioid/dopamine release

• engaging ———

• receptors on the medium spiny neurons

Other psychoactive drugs influence the activity of neurons within the nucleus accumbens (NA) by:

• modulating opioid/dopamine release

• engaging receptors on the medium spiny neurons

• or by influencing the ———- that regulate neural activity

• inhibitory action of GABAergic neurons

Neurons within the nucleus accumbens also receive input from other regions, such as the cortex. These neurons release the (excitatory/inhibitory?) neurotransmitter glutamate. 

excitatory

Neurons within the nucleus accumbens also receive input from other regions, such as the cortex. These neurons release the excitatory neurotransmitter glutamate. Changes in how a postsynaptic cell responds to glutamate can produce a ——— in how a neural circuit operates, a physiological alteration that has been linked to learning and memory.

(a) lasting change (e.g., a long-term potentiation)

(Within the nucleus accumbens)

• cortical neurons that release glutamate provide a rich input to the nucleus accumbens, an input that is thought to ——-

carry information about the specific details of the sensory systems engaged

(Within the nucleus accumbens)

• cortical neurons that release glutamate provide a rich input to the nucleus accumbens, an input that is thought to carry information about the specific details of the sensory systems engaged.

• At the same time, dopaminergic input on to these neurons provides a——

diffuse input that can signal the motivational state of the organism

(Within the nucleus accumbens)

• cortical neurons that release glutamate provide a rich input to the nucleus accumbens, an input that is thought to carry information about the specific details of the sensory systems engaged.

• At the same time, dopaminergic input on to these neurons provides a diffuse input that can signal the motivational state of the organism.

  • When paired, this dopaminergic input may help select ——

the relevant pattern of glutamatergic input

(Within the nucleus accumbens)

• cortical neurons that release glutamate provide a rich input to the nucleus accumbens, an input that is thought to carry information about the specific details of the sensory systems engaged.

• At the same time, dopaminergic input on to these neurons provides a diffuse input that can signal the motivational state of the organism.

  • When paired, this dopaminergic input may help select the relevant pattern of glutamatergic input, acting as a kind of teacher that binds sensory attributes with reward value, thereby ——-

enhancing the motivational significance of these cues

When does the dopaminergic teacher instruct the nucleus accumbens to learn? - To answer this question, researchers have examined neural activity in monkeys while they work for reward (e.g., a sip of fruit juice).

The expected reward, itself, produced no effect. If, however, the expected reward was omitted, there was an inhibition of neural activity at the time of reward. What these observations suggest is that dopamine activity does not simply report whether or not a reward has occurred.

Instead, dopamine activity seems to code the “———-”→ the deviation between what the animal received and what it expected :

• Dopamine response = Reward occurred – Reward predicted
  

“reward prediction error”

When does the dopaminergic teacher instruct the nucleus accumbens to learn? - To answer this question, researchers have examined neural activity in monkeys while they work for reward (e.g., a sip of fruit juice).

The expected reward, itself, produced no effect. If, however, the expected reward was omitted, there was an inhibition of neural activity at the time of reward. What these observations suggest is that dopamine activity does not simply report whether or not a reward has occurred.

Instead, dopamine activity seems to code the “reward prediction error”— the deviation between what the animal received and what it expected :

• — —-?——-
  

• Dopamine response = Reward occurred – Reward predicted

The notion that learning is a function of the discrepancy between what the animal received, and what it expected, parallels the learning rule posited by Rescorla and Wagner (1972).

As discussed in Chapter 4, learning appears to occur when an event is unexpected. The best example of this is observed in the blocking paradigm, where prior learning that one cue (e.g., a tone) predicts the US blocks learning about an added cue (e.g., a light).

Interestingly, dopaminergic neurons within the ventral tegmentum exhibit this phenomenon, producing a burst of activity to the originally paired cue but not the added one. Notice too that this represents another instance in ————

which a portion of the midbrain (the VTA) acts as an informed instructor, to promote learning within the forebrain.

The notion that learning is a function of the discrepancy between what the animal received, and what it expected, parallels the learning rule posited by Rescorla and Wagner (1972).

As discussed in Chapter 4, learning appears to occur when an event is unexpected. The best example of this is observed in the blocking paradigm, where prior learning that one cue (e.g., a tone) predicts the US blocks learning about an added cue (e.g., a light).

Interestingly, dopaminergic neurons within the ventral tegmentum exhibit this phenomenon, producing a burst of activity to the originally paired cue but not the added one. Notice too that this represents another instance in which a portion of the midbrain (the VTA) acts as an informed instructor, to promote learning within the forebrain.

An analogous function was ascribed earlier to the——- and ——

periaqueductal gray (Box 4.x) and dorsal raphe nucleus (Box 5.x).

bused drugs may encourage a cycle of dependency because they have a pharmacological advantage.

For example, psychostimulants artificially drive dopaminergic activity, and in this way act as a kind of Trojan horse that fools the nervous system, producing ——

a spike in dopamine activity that the brain interprets as a positive prediction error

psychostimulants artificially drive dopaminergic activity, and in this way act as a kind of Trojan horse that fools the nervous system, producing a spike in dopamine activity that the brain interprets as a positive prediction error

This reinforces new learning and links the ——— to ——-, giving them a motivational value that fuels the acquired drug craving and predisposes an addict to relapse

sensory cues associated with drug administration (to) reward

cues associated with drug consumption acquire an ——- that can fuel drug craving.

incentive value

Interestingly, the craving that fuels drug taking appears to be —— and ——- distinct from the process that underlies how much we consciously “like” an addictive substance

physiologically (and) psychologically (distinct)

Liking is related to the —- state elicited by reward and can be inferred behaviorally from facial expressions.

hedonic

Interestingly, microinjecting an opioid into small regions (————) of the nucleus accumbens enhances signs of liking

(hedonic hot spots)

A second hedonic hot spot has been identified within an adjoining region, the ——

ventral pallidum (VP)

ventral pallidum (VP) hedonic hot-spot:

Here too, local infusion of an —— enhances the liking response to a sweet solution

opioid agonist

(Hedonic hot-spots)

Observations such as these have led researchers to suggest that the pleasurable component of reward is linked to opioid activity within the ——- and ——

nucleus accumbens and vental pallidum

T/F: the complete destruction of dopaminergic neurons innervating the nucleus accumbens had no effect on opioid-induced liking

TRUE

T/F: liking reactions to sweet tastes ARE elicited by manipulations that engage dopaminergic neurons

FALSE

the complete destruction of dopaminergic neurons innervating the nucleus accumbens had no effect on opioid-induced liking & liking reactions to sweet tastes are not elicited by manipulations that engage dopaminergic neurons.

These observations suggest that dopamine activity is——

neither required (necessary) nor sufficient to generate liking.

self administration of a psychostimulant is blocked by ——— or ——-

pretreatment with a dopamine antagonist (or) a physiological manipulation that destroys dopaminergic neurons in this region.

self administration of a psychostimulant is blocked by pretreatment with a dopamine antagonist or a physiological manipulation that destroys dopaminergic neurons in this region.

Across a range of tasks, in the absence of dopamine, rats cannot ——

use information about rewards to motivate goal-directed behavior; they cannot act on their preferences.

Robinson and Berridge have suggested that manipulations of the dopamine system affect motivation because they——

impact a distinct quality of reward

Rather than influencing how much the animal consciously likes the reward, they propose that dopamine activity is coupled to an unconscious process that they call——

wanting

Robinson and Berridgee see wanting as related to the underlying motivational value of the reward, encoding ——-

the degree to which the organism is driven to obtain and consume the reward independent of whether consumption engenders pleasure.

cues paired with reward gain an ——- that drives a form of wanting, transforming sensory signals of reward into attractive, desired goals.

incentive salience

cues paired with reward gain an incentive salience that drives a form of wanting, transforming sensory signals of reward into attractive, desired goals.

These cues act as motivational magnets that unconsciously—-

pull the animal to approach the reward

a —— engages dopamine activity and acts as a teacher, fostering the association of sensory cues with reward.

(a) positive prediction error

a positive prediction error engages dopamine activity and acts as a teacher, fostering the association of sensory cues with reward.

From this view, dopamine activity within the nucleus accumbens binds the —— of a goal to motivation, driving the wanting that can fuel drug craving.

hedonic properties

a positive prediction error engages dopamine activity and acts as a teacher, fostering the association of sensory cues with reward.

From this view, dopamine activity within the nucleus accumbens binds the hedonic properties of a goal to motivation, driving the wanting that can fuel drug craving.

Supporting this, research has shown that drug paired cues acquire conditioned value and will support new instrumental learning in a —-transfer test.

Pavolian-to-instrumental

a positive prediction error engages dopamine activity and acts as a teacher, fostering the association of sensory cues with reward.

From this view, dopamine activity within the nucleus accumbens binds the hedonic properties of a goal to motivation, driving the wanting that can fuel drug craving.

Supporting this, research has shown that drug paired cues acquire conditioned value and will support new instrumental learning in a Pavolian-to-instrumental transfer test.

This effect depends on ——-

dopamine activity and learning within the basolateral amygdala