The rewarding efficacy of brain stimulation and its modulation by dopaminergic drugs in young adult and old BN F344F1 rats.
In old age there is evidence of waning motivation, and possibly lowering of mood. Physiologically there is a decline in the levels of brain neurotransmitters such as acetylcholine and dopamine, and loss of myelin. These changes might be expected to impair the functioning of brain circuitry for reinforcement, and to lead to impaired motivation. To evaluate the function of brain reinforcement mechanisms during aging we examined brain stimulation reward and its modulation by dopaminergic drugs in BN F344F1 rats aged from young adult (5 months) to old (37 months). Brain stimulation directly activates the neural circuitry for reinforcement, and the response rate-frequency tradeoff can be used to characterize the functioning of the system. Both young and old subjects readily learned to lever press for 0.6 s trains of 0.15 ms brain stimulation pulses, and there was no difference in the number of pulses per train required to maintain responding at 50% of the maximum rate (M50). Amphetamine (0.5 mg/kg) significantly reduced the M50, and the dopamine synthesis inhibitor alpha-methyl-p-tyrosine (100 mg/kg) increased the M50, but these effects were not influenced by the age of the subjects. The results suggest that in healthy animals dopaminergic modulation of reinforcement is functionally intact in old age.
Sonnenschein
Bonnie
B
Department of Psychology, McGill University, 1205 Dr. Penfield Avenue, Montreal, Quebec, Canada H3A 1B1.
Franklin
Keith B J
KB
D000375:Aging / Q000523:psychology*; D000818:Animals; D001921:Brain / Q000502:physiology*; D001923:Brain Chemistry / Q000187:drug effects; D003216:Conditioning, Operant / Q000187:drug effects* / Q000502:physiology*; D003913:Dextroamphetamine / Q000494:pharmacology; D015259:Dopamine Agents / Q000494:pharmacology*; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D051381:Rats; D011916:Rats, Inbred F344; D012055:Reinforcement Schedule; D012201:Reward; D019805:alpha-Methyltyrosine / Q000494:pharmacology
D015259:Dopamine Agents; D018765:Dopamine Uptake Inhibitors; D004791:Enzyme Inhibitors; D019805:alpha-Methyltyrosine; D003913:Dextroamphetamine