Behavioral and frontal cortical metabolic effects of apomorphine and muscimol microinjections into the mediodorsal thalamic nucleus

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Abstract
To study sensorimotor correlates of dopamine (DA) and gammaamino butyric acid (GABA) neurotransmission in the thalamus, we microinjected the DA agonist apomorphine (APO), the GABA agonist muscimol and vehicle into the mediodorsal thalamic nucleus (MdT) of rats and monitored catalepsy, sensorimotor asymmetries and the acoustic startle response. Unilateral MdT muscimol microinjections (50 ng) produced a lateralization of the removal of adhesive disks placed simultaneously on both forelegs in a tactile extinction task, but did not measurably influence any aspects of startle behavior. The sensorimotor asymmetry consisted of preferential orientation to the adhesive disk on the side ipsilateral to the microinjection. Vehicle and APO microinjections produced no significant behavioral results. In a follow-up study, unilateral MdT muscimol microinjections significantly depressed medial prefrontal cortical metabolism (measured by 2-fluorodeoxyglucose uptake) by 24%, but did not affect nucleus accumbens metabolic activity. Together, these findings are consistent with the concept that GABA-mediated inhibition of thalamocortical neurons in the MdT influences tactile extinction behavior, most likely by selectively suppressing excitatory input to the frontal cortex. The sensorimotor asymmetry observed in the present study resembles attentional and spatial memory deficits associated with frontal cortical lesions, and in conjunction with the 2-fluorodeoxyglucose results, suggests that elevated GABA neurotransmission in the thalamus may be involved in attentional and functional metabolic deficits in humans.