Reversal of 6HD-induced neonatal brain catecholamine depletion after operant training

Kinetic assessment of the effects of task difficulty, microencephaly, and a response manipulandum alteration on the rate of fixed-ratio discrimination acquisition.

“…The FRD task is an arbitrary matching-to-sample or a conditional discrimination task. Animals were trained to learn and perform FRD as in previous studies in our laboratory (Loupe et al, 1995; Stodgell et al, 1998; Stodgell, Schroeder, & Tessel, 1996; Tessel et al, 1995). The apparatuses used were 29 cm × 25.3 cm × 28 cm experimental operant chambers housed in larger insulated shells with ventilation fans and operated via computer (Coulbourn Instruments Co., Allentown, PA).…”

“…Furthermore, we have investigated the capacity of fixed-ratio discrimination training (FRDT) to antagonize brain damage and its behavioral consequences in rat models of human disease (e.g., Loupe, Schroeder, & Tessel, 1995; Tessel, Schroeder, Loupe, & Stodgell, 1995). The FRD task is a conditional discrimination task in which an organism is required to discriminate between two quantitatively different fixed-ratio (FR) response requirements each completed on a single designated lever.…”

“…Reducing the numerical difference between the two FR values to be discriminated easily increases FRD difficulty. We have shown that FRDT involving incrementally more difficult FRDs antagonizes prenatally induced hippocampal hypoplasia in the adult microencephalic rat (Loupe et al, 1995), reverses neonatally 6-hydroxydopamine-induced striatal dopamine depletion in adult rat models of Lesch-Nyhan disease (Stodgell, Loupe, Schroeder, & Tessel, 1998; Tessel et al, 1995), and normalizes behavioral hypersensitivity to the mixed dopamine receptor agonist apomorphine in a 6-hydroxydopamine dopamine-depleted rat model of Parkinson's disease (Van Keuren, Stodgell, Schroeder, & Tessel, 1998).…”

Self‐injurious behavior: Gene–brain–behavior relationships

“…Both treatments markedly deplete brain dopamine tissue contents in what had been thought to be an irreversible manner. Tessel et al [1995aTessel et al [ , 1995b demonstrated that at least such depletions and/or their behavioral consequences are not irreversible; indeed, such reversals can be generated simply by subjecting adult LNS and PD rats to one form of prolonged conditional discrimination training (fixed-ratio discriminations, FRD). Consequently, such training appears to function as a nonpharmacological, nonsurgical means to replace the lost dopamine with endogenous dopamine by "exercising" residual brain dopaminergic neurons.…”