Subthalamic responses to amphetamine and apomorphine in the behaving rat with a unilateral 6-OHDA lesion in the substantia nigra.
The activity of neurons in the subthalamic nucleus (STN) of the behaving rat, before and after a unilateral 6-OHDA lesion of the substantia nigra, was recorded with the extracellular technique to determine whether it was altered following systemic amphetamine, 5 mg/kg, apomorphine, 3 mg/kg, and apomorphine, 0.3 mg/kg, and whether in cases of altered activity, it was related to the drug-induced motor response expressed concurrently. Activity in the STN of intact rats increased dramatically after amphetamine, 5 mg/kg. This excitatory response had the same latency, similar magnitude, and the same duration as the motor response expressed in terms of locomotion and oral stereotypy. Motor and unit responses were also induced by amphetamine after the lesion with 6-hydroxydopamine (6-OHDA), but now the excitatory response was attenuated while the motor response was not. The effects of the 6-OHDA lesion were the same in all animals with loss of the nigra dopamine neurons, regardless of whether they were rotators or non-rotators. Activity in the STN of intact rats also increased after apomorphine, 3 mg/kg, and again, this increase was correlated with the increase in motor behavior, but both responses were of shorter duration than the responses to amphetamine. The increases in unit activity and motor behavior induced by apomorphine in the 6-OHDA-lesioned rats had the same magnitude but lasted longer than in the intact rats. Treatment with apomorphine, 0.3 mg/kg, of the intact rats produced small and very brief increases in the activity of the STN and in motor behavior. The same treatment given the 6-OHDA-lesioned rats produced responses of larger magnitude but no change in duration. These findings demonstrate a role for STN neurons in the mediation of the motor behaviors induced by stimulation of the dopamine receptor. The results also show that a unilateral lesion of the substantia nigra with 6-OHDA did not block these responses but altered them in a manner consistent with a dopaminergic deafferentation of the basal ganglia. The increased activity in the STN during the expression of dopamine-dependent motor behavior conflicts with the current model of basal ganglia function that assumes prejudicial effects of excessive STN activity on the expression of motor behavior. An explanation for this conflict suggests that it is more apparent than real.
Olds
M E
ME
Division of Biology, 156-29, California Institute of Technology, Pasadena, California 91125, USA. olds@its.caltech.edu
Jacques
D B
DB
Kopyov
O
O
D000200:Action Potentials / Q000502:physiology; D018663:Adrenergic Agents / Q000494:pharmacology; D000661:Amphetamine / Q000494:pharmacology*; D000818:Animals; D001058:Apomorphine / Q000494:pharmacology*; D018491:Dopamine Agonists / Q000494:pharmacology; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains; D013378:Substantia Nigra / Q000503:physiopathology*; D020531:Subthalamic Nucleus / Q000187:drug effects* / Q000502:physiology*; D013997:Time Factors
D018663:Adrenergic Agents; D018491:Dopamine Agonists; D000661:Amphetamine; D001058:Apomorphine