* Cocaine-elicited imbalances in ventromedial prefrontal cortex Homer1 versus Homer2 expression: implications for relapse.
- Withdrawal from a history of extended access to self-administered cocaine produces a time-dependent intensification of drug seeking, which might relate to a cocaine-induced imbalance in the relative expression of constitutively expressed Homer1 versus Homer2 isoforms within the ventromedial aspect of the prefrontal cortex (vmPFC). Thus, we employed immunoblotting to examine the relation between cue-reinforced lever pressing at 3- versus 30-day withdrawal from a 10-day history of extended access (6 hours/day) to intravenous cocaine (0.25 mg/infusion) or saline (Sal6h), and the expression of Homer1b/c and Homer2a/b within the vmPFC versus the more dorsomedial aspect of this structure (dmPFC). Behavioral studies employed adeno-associated virus (AAV) vectors to reverse cocaine-elicited changes in the relative expression of Homer1 versus Homer2 isoforms and tested animals for cocaine prime-, and cue-induced responding following extinction training. Cocaine self-administration elevated both Homer1b/c and Homer2a/b levels within the vmPFC at 3-day withdrawal, and the rise in Homer2a/b persisted for at least 30 days. dmPFC Homer levels did not change as a function of self-administration history. Reversing the relative increase in Homer2 versus Homer1 expression via Homer1c overexpression or Homer2b knockdown failed to influence cue-reinforced lever pressing when animals were tested in a drug-free state, but both AAV treatments prevented cocaine-primed reinstatement of lever-pressing behavior. These data suggest that a cocaine-elicited imbalance in the relative expression of constitutively expressed Homer2 versus Homer1 within the vmPFC is necessary for the capacity of cocaine to reinstate drug-seeking behavior, posing drug-induced changes in vmPFC Homer expression as a molecular trigger contributing to drug-elicited relapse.
Overview of noun level
The noun level has 8 senses (first 6 from tagged texts)
1. (69) degree, grade, level -- (a position on a scale of intensity or amount or quality; "a
moderate grade of intelligence"; "a high level of care is required"; "it is all a matter of degree")
2. (22) grade, level, tier -- (a relative position or degree of value in a graded group; "lumber of
the highest grade")
3. (15) degree, level, stage, point -- (a specific identifiable position in a continuum or series or
especially in a process; "a remarkable degree of frankness"; "at what stage are the social
sciences?")
4. (5) level -- (height above ground; "the water reached ankle level"; "the pictures were at the
same level")
5. (1) level, spirit level -- (indicator that establishes the horizontal when a bubble is centered
in a tube of liquid)
6. (1) horizontal surface, level -- (a flat surface at right angles to a plumb line; "park the car
on the level")
7. level, layer, stratum -- (an abstract place usually conceived as having depth; "a good actor
communicates on several levels"; "a simile has at least two layers of meaning"; "the mind functions
on many strata simultaneously")
8. floor, level, storey, story -- (a structure consisting of a room or set of rooms at a single
position along a vertical scale; "what level is the office on?")
Overview of verb level
The verb level has 6 senses (first 3 from tagged texts)
1. (4) level -- (aim at; "level criticism or charges at somebody")
2. (1) level, raze, rase, dismantle, tear down, take down, pull down -- (tear down so as to make
flat with the ground; "The building was levelled")
3. (1) flush, level, even out, even -- (make level or straight; "level the ground")
4. charge, level, point -- (direct into a position for use; "point a gun"; "He charged his weapon at
me")
5. level -- (talk frankly with; lay it on the line; "I have to level with you")
6. level, level off -- (become level or even; "The ground levelled off")
--- WordNet end ---