da 2 Flashcards
intracranial self stimulation
electrical self stimulation extremely sensitive to elecrode location
midbrain dopaminergic neurons project from vta to nac
medial forebrain bundle MFB contains axons of VTA neurons projecting to the nac - very effective target for self stimulation
hedonic hotspots of the nAC - what does activation of the nac do
electrical and pharmacological manipulation of NAc alters responses to bth rewarding and aversive stimuli,
afferent projections to the nac about what the stimulus is
amygdala, prefrontal cortex and hippocampus
afferent projections to NAc- that the stimulus is rewarding
the ventral tegmental area
outputs of the NAc
two functionally distinct output pathways
Pre motor related output
- dorsolateral ventral pallium
- substantia nigra pars reticulata
Reward/ emotion related output
- ventromedial ventral pallidum
- substantia innominate (part of the amygdala
- lateral hypothalamus
what does dopamine do
D1 acivates adenylyl cyclase increasing concentration of cAMP
D2- inhibits adenylyl cyclase, decreasing intracellular concentration of cAMP.
what pathway is associated with reward
evidence points towards a crucial role of the mesolimbic dopamine pathway in reward processing
- operant conditioning
- classical conditioning
- primary rewards
- exposure to females
- goal directed behaviour
why look at drugs of abuse
reward is associated with increased dopamine concentration in the nucleus accumbens therefore substances that hijack reward systems should target the NAc.
cocaine action in the NAc
Normal DA transmission
- DA released from presynaptic neuron
- increased da in cleft
- da binds to post synaptic neuron
- excess da removed by DAT (requires NA)
cocaine action
- cocaine blocks binding site of NA on DAT
- reuptake of DA is blocked- stays in synaptic cleft
- continues to agonise Post synaptic neuron
Amphetamine action in the NAc
- amph is a substate of DAT and competitively inhibits DA reuptake
Amph gets transported into presynaptic neuron- depletes vesicles of DA
this promotes DAT mediated reverse transport. independent of AP
Opiod action at the VTA
- opiods target u-opiod receptos (MORs) that are in the VTA located excusively on GABA interneurons
activation of MOR inhibits gaba release.
GABA is inhibitory- so stopping it means more DA release.
cannabis action at VTA interneurons
- THC binds to Cb1Rs. inhibiting the release of GABA.
Disinhibition increases firing towards nac.
nicotine action at VTA
- causes direct excitation of DA neurons in VTA by activating ionotropic ACh nicotinic receptors
