Adrenergic transmission facilitates extinction of conditional fear in mice.
|Title||Adrenergic transmission facilitates extinction of conditional fear in mice.|
|Publication Type||Journal Article|
|Year of Publication||2004|
|Authors||Cain, CK, Blouin AM, Barad M|
|Journal||Learning & memory (Cold Spring Harbor, N.Y.)|
|Date Published||2004 Mar-Apr|
|Keywords||Adrenergic Agonists, Animals, Association Learning, Conditioning, Classical, Extinction, Psychological, Fear, Immobility Response, Tonic, Male, memory, Mice, Mice, Inbred C57BL, Norepinephrine, Propranolol, Synaptic Transmission, Yohimbine|
Extinction of classically conditioned fear, like its acquisition, is active learning, but little is known about its molecular mechanisms. We recently reported that temporal massing of conditional stimulus (CS) presentations improves extinction memory acquisition, and suggested that temporal spacing was less effective because individual CS exposures trigger two opposing processes: (1) fear extinction, which is favored by CS massing, and (2) fear incubation (increase), which is favored by spacing. We here report the effects of manipulating the adrenergic system during massed or spaced CS presentations in fear-conditioned mice. We administered yohimbine (5 mg/kg), an alpha(2)-receptor antagonist, or propranolol (10 mg/kg), a beta-receptor antagonist, systemically prior to CS presentation sessions and recorded both short- and long-term changes in conditional freezing. Yohimbine treatment facilitated extinction of both cue and context fear with massed protocols. When given before spaced CS presentations, propranolol led to a persistent incubation of cue fear, whereas yohimbine led to persistent extinction, compared with vehicle-treated animals, which showed no change in fear. These results suggest that norepinephrine positively modulates the formation of fear extinction memories in mice. They also provide clear evidence that spaced CS presentations trigger both fear-reducing (extinction) and fear-increasing (incubation) mechanisms.
|Alternate Journal||Learn. Mem.|