Electrophysiological and behavioral output of the rat basal ganglia after intrastriatal infusion of d-amphetamine: lack of support for the basal ganglia model.
Dopamine, by acting upon D1 and D2 dopamine receptors located on striatonigral and striatopallidal neurons, respectively, has been postulated to inhibit output from the substantia nigra pars reticulata (SNpr) and internal pallidal segment (GPi). The inhibition of the SNpr/GPi should, in turn, disinhibit the thalamus to facilitate movement. The present study tests this prediction in intact (unlesioned) rats by attempting to correlate changes in the single unit activities of SNpr neurons with motor (i.e. behavioral) responses in the 20-30 min after infusions of d-amphetamine into the striatum. Unilateral injections of amphetamine (20 microg/microl) into either the dorsal-rostral, central, or ventral-lateral striatum failed to appreciably alter behavior and, in parallel electrophysiological studies, failed to consistently or significantly alter the activities of SNpr neurons in either chloral hydrate-anesthetized rats or awake locally anesthetized rats. However, when amphetamine was infused bilaterally into the ventral-lateral striatum (VLS; 20 microg/microl per side), a robust behavioral activation ensued (increased locomotor activity, oral movements, and sniffing) with an onset ranging from immediate to 20 min post-infusion and persisting for at least 40 min. In parallel studies, bilateral amphetamine infusions into VLS also caused changes in the firing frequency of a majority of SNpr neurons. However, the changes in firing were extremely variable and, contrary to expectation, the net population response of SNpr neurons was an increase in firing which corresponded in time with the period of peak behavioral activation. These results show that (i) bilateral but not unilateral activation of striatal dopamine receptors is needed to elicit behavioral and electrophysiological output from the basal ganglia, and (ii) motor activation is apparently not signaled by a generalized inhibition of SNpr firing, as is predicted by the basal ganglia model.
Waszczak
B L
BL
Department of Pharmaceutical Sciences, Physical Therapy and Psychology, Northeastern University, 360 Huntington Avenue, Boston, MA 02115, USA. b.waszczak@neu.edu
Martin
L
L
Boucher
N
N
Zahr
N
N
Sikes
R W
RW
Stellar
J R
JR
D000818:Animals; D001479:Basal Ganglia / Q000502:physiology*; D001522:Behavior, Animal / Q000502:physiology*; D001931:Brain Mapping; D000697:Central Nervous System Stimulants / Q000008:administration & dosage / Q000494:pharmacology*; D003913:Dextroamphetamine / Q000008:administration & dosage / Q000494:pharmacology*; D018765:Dopamine Uptake Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D004594:Electrophysiology; D008297:Male; D008845:Microinjections; D008959:Models, Neurological; D017072:Neostriatum / Q000502:physiology*; D009476:Neurons, Efferent / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D017447:Receptors, Dopamine D1 / Q000187:drug effects; D017448:Receptors, Dopamine D2 / Q000187:drug effects
D000697:Central Nervous System Stimulants; D018765:Dopamine Uptake Inhibitors; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D003913:Dextroamphetamine