Dopamine neurons in the ventral tegmental area fire faster in adolescent rats than in adults.
Adolescence may be a period of vulnerability to drug addiction. In rats, elevated firing activity of ventral tegmental area (VTA) dopamine neurons predicts enhanced addiction liability. Our aim was to determine if dopamine neurons are more active in adolescents than in adults and to examine mechanisms underlying any age-related difference. VTA dopamine neurons fired faster in adolescents than in adults as measured with in vivo extracellular recordings. Dopamine neuron firing can be divided into nonbursting (single spikes) and bursting activity (clusters of high-frequency spikes). Nonbursting activity was higher in adolescents compared with adults. Frequency of burst events did not differ between ages, but bursts were longer in adolescents than in adults. Elevated dopamine neuron firing in adolescent rats was also observed in cell-attached recordings in ex vivo brain slices. Using whole cell recordings, we found that passive and active membrane properties were similar across ages. Hyperpolarization-activated cation currents and small-conductance calcium-activated potassium channel currents were also comparable across ages. We found no difference in dopamine D2-class autoreceptor function across ages, although the high baseline firing in adolescents resulted in autoreceptor activation being less effective at silencing neurons. Finally, AMPA receptor-mediated spontaneous excitatory postsynaptic currents occurred at lower frequency in adolescents; GABA(A) receptor-mediated spontaneous inhibitory postsynaptic currents occurred at both lower frequency and smaller amplitude in adolescents. In conclusion, VTA dopamine neurons fire faster in adolescence, potentially because GABA tone increases as rats reach adulthood. This elevation of firing rate during adolescence is consistent with it representing a vulnerable period for developing drug addiction.
Department of Cellular and Molecular Pharmacology, Rosalind Franklin University, North Chicago, Illinois, USA. mccutcheon.james@gmail.com
James E
JE
McCutcheon
Kelly L
KL
Conrad
Steven B
SB
Carr
Kerstin A
KA
Ford
Daniel S
DS
McGehee
Michela
M
Marinelli
D000200:Action Potentials; D000367:Age Factors; D000818:Animals; D059290:Dopaminergic Neurons / Q000502:physiology*; D019706:Excitatory Postsynaptic Potentials; D053444:Inhibitory Postsynaptic Potentials; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D018091:Receptors, AMPA / Q000502:physiology; D017448:Receptors, Dopamine D2 / Q000502:physiology; D018079:Receptors, GABA / Q000502:physiology; D051640:Small-Conductance Calcium-Activated Potassium Channels / Q000502:physiology; D017557:Ventral Tegmental Area / Q000254:growth & development / Q000502:physiology*
D018091:Receptors, AMPA; D017448:Receptors, Dopamine D2; D018079:Receptors, GABA; D051640:Small-Conductance Calcium-Activated Potassium Channels