Neonatal and adult forebrain norepinephrine depletion and the behavioral and cortical thickening effects of enriched/impoverished environment

Two experiments examined the effects of neonatal or adult intracerebral injections of 6-hydroxydopamine (6-OHDA) on the effects of enriched (ENR) vs. impoverished (IMP) housing conditions. In Expt. 1, neonatal rats received intraventricular injections of 6-OHDA after pretreatment with buproprion to destroy norepinephrine (NE) terminals while lessening damage to dopamine (DA) terminals. The rats were subsequently raised in either enriched or impoverished environments and then tested for their spatial problem-solving ability in an automated Hebb-Williams maze. Littermates did not undergo this testing but were instead assessed for cortical thickness. Despite the substantial depletion of NE in the forebrains of the 6-OHDA-treated rats, they responded to enriched rearing as did the control rats, i.e., they solved the Hebb-Williams problems more efficiently than their impoverished reared counterparts and they showed thicker cortices. In Expt. 2, adult rats received 6-OHDA lesions of the dorsal noradrenergic bundle and were then relegated to enriched or impoverished housing for 42 days. Subsequently, the enriched-housed rats solved the Hebb-Williams mazes more efficiently than their impoverished-housed counterparts and this effect of housing was not altered by the dorsal bundle lesion which severely depleted forebrain NE. These two experiments do not support a role for forebrain NE in the alteration of the rat cortex and behavior by environmental enrichment. It was concluded that the cognitive effects of enriched rearing do not require intact forebrain NE but that they may be influenced by the peripheral sympathectomy that is one consequence of neonatal systemic 6-OHDA injections.