Facilitation of fear extinction by midbrain periaqueductal gray infusions of RB101(S), an inhibitor of enkephalin-degrading enzymes.

The midbrain periaqueductal gray and fear extinction: opioid receptor subtype and roles of cyclic AMP, protein kinase A, and mitogen-activated protein kinase.

Four experiments studied the opioid receptor subtype and signal transduction mechanisms mediating fear extinction in the ventrolateral quadrant of the midbrain periaqueductal gray (vlPAG). Microinjection of a mu- but not a delta- or kappa-opioid receptor antagonist into the vlPAG retarded extinction. Extinction was also dose-dependently retarded by vlPAG infusions of a cyclic AMP (cAMP) analog ...

Opioid receptors in the midbrain periaqueductal gray regulate extinction of pavlovian fear conditioning.

Four experiments studied the role of opioid receptors in the midbrain periaqueductal gray matter (PAG), an important structure eliciting conditioned fear responses, in the extinction of Pavlovian fear. Rats received pairings of an auditory conditioned stimulus (CS) with a foot shock unconditioned stimulus (US). The freezing conditioned response (CR) elicited by the CS was then extinguished via ...

RB101-mediated protection of endogenous opioids: potential therapeutic utility?

The endogenous opioids met- and leu-enkephalin are inactivated by peptidases preventing the activation of opioid receptors. Inhibition of enkephalin-degrading enzymes increases endogenous enkephalin levels and stimulates robust behavioral effects. RB101, an inhibitor of enkephalin-degrading enzymes, produces antinociceptive, antidepressant, and anxiolytic effects in rodents, without typical opi...

Role of Amygdala-Infralimbic Cortex Circuitry in Glucocorticoid-induced Facilitation of Auditory Fear Memory Extinction

Introduction: The basolateral amygdala (BLA) and infralimbic area (IL) of the medial prefrontal cortex (mPFC) are two interconnected brain structures that mediate both fear memory expression and extinction. Besides the well-known role of the BLA in the acquisition and expression of fear memory, projections from IL to BLA inhibit fear expression and have a critical role in fear extinction. Howev...

The effects of optogenetic inhibition of ventrolateral periaqueductal gray on the acquisition and extinction of contextual fear learning in rats