Neural plasticity STUDIES Flashcards
Robinson & Kolb (1999)
Repeated cocaine injections leads to increased dendritic spine density, length and branching in accumbens neurons
Very long lasting changes
Badiani et al. (1995)
Drug effects are influenced by set and setting - when only place changes (& dose stays the same)
Li et al. (2004)
Context influences cocaine’s ability to reorganise synaptic connectivity
Crombag et al. (2005)
Rats will reliably self-administer sucrose and amphetamine
Found that after 30 days of active lever pressing, only amphetamine alters morphology of dendrites on NAc neurons
Supported by Robinson et al. (2001)
Bell & Kalivas (2000)
Environment modulates cocaine-induced glutamate release in NAc
Glutamate release enhanced when given cocaine in the same environment
Boudreau & Wolf (2005)
Repeated cocaine increases AMPAR surface expression
Called time-dependent regulation
Kauer et al. (1988)
Assessing synaptic strength through AMPAR/NMDAR ratio
A > N leads to increased synaptic strength
Kourrich et al. (2007)
Daily cocaine injections over 5 days
Found cocaine-induced increase in accumbens synaptic strength is time-dependent (i.e. repeated injections are needed to see change)
Sesack & Grace (2010) review
Inputs come from PFC, hippocampus and amygdala
Wanted to investigate whether AMPAR/NMDAR ratio changes occurs at an input-specific manner
Britt et al. (2002)
AMPAR/NMDAR ratio are increased at hippocampal inputs, not PFC or amygdala
Ungless et al. (2001)/Borgland et al. (2004)
Single cocaine injection causes massive increase in AMPA/NMDAR ratio
Thus acute, short lasting changes can be seen with single cocaine injections
A “transient” change in the VTA
Chen et al. (2008)
Cocaine (but not food or sucrose) self-admin persistently increases synaptic strength in the VTA
Drugs are more persistent than natural rewards
DeRoache-Gamonet at al. (2004)
Long-term study over course of 70 days
D1-D70 cocaine self-administration with progressive ratio schedule
Rats became drug free at D70 and relapse test occurred to split rats into ‘high’ and ‘low’ relapse rats
After split, behaviour was retrogradely examined;
- found no behavioural differences at early self-admin stage
- at late self-admin stage; high relapse rats scored higher on all three behaviours;
1) difficulty stopping
2) high motivation for drug
3) drug persistence in face of -ve consequences
Repeated study after 30 drug free days and found high relapse rats remained high relapse (similar to relapse behaviour in human addicts)
Kasanetz et al. (2010)
Measured LTD (down regulation) of AMPAR/NMDAR following prolonged cocaine self-administration over 50 days
Non addicts had normal LTD, but addicts had impaired LTD in the glutamate system
Concluded this impaitment could be why addicts are incapable of controlling drug taking
Conrad et al. (2008)
Long term withdrawal from cocaine self-administration is associated with increased cocaine-seeking and altered AMPAR composition in accumbens neuron
Glu2 lacking AMPARs are found after ‘addiction’ is created
Drug-wanting builds up over 45 drug free days
At D45, is NASPM (AMPAR antagonist) administered then cocaine seeking behaviour is disrupted
Argue Glu2 lacking AMPAR causes cocaine seeking behaviour
