Alteration of the PKA-CREB cascade in the mPFC accompanying prepulse inhibition deficits: evidence from adolescent social isolation and chronic SKF38393 injection during early adolescence

Prepulse inhibition (PPI) refers to the inhibition of the startle reflex that occurs when the startling stimulus is preceded by a weak prestimulus. Altered adolescent mPFC circuitry induced by early-life adversity might be a key source of PPI deficits. The current study focused on variations in the cyclic AMP (cAMP)/protein kinase A (PKA)-cAMP-response element-binding protein (CREB) pathway in the medial prefrontal cortex (mPFC). We found a negative relationship between PPI and the PKA-CREB cascade during adolescence by employing both developmental and pharmacologic manipulations. Experiment 1, with the early adolescent social isolation model [postnatal days (PNDs), 21–34), displayed a disrupted PPI at PND 35 and significantly altered PKA, phosphorylated CREB (p-CREB) and the ratio of p-CREB to CREB. In particular, the level of p-CREB was negatively related to PPI performance. In Experiment 2, SKF38393, a well-characterized activator of adenylate cyclase and cAMP/PKA, was chronically injected during early adolescence (PNDs 28–34). We sought to mimic potential biochemical changes, particularly PKA activation, which is possibly altered by adolescent social isolation, and to determine if PPI was disrupted, similar to the disruption associated with adolescent social isolation. On PND 35, PPI deficits were detected, as well as increased PKA, marginally increased CREB and no change occurred in p-CREB or the ratio of p-CREB to CREB. In particular, PKA activity was negatively rel...
Source: Behavioural Pharmacology - Category: Drugs & Pharmacology Tags: Research Reports Source Type: research