Ketamine and amphetamine both enhance synaptic transmission in the amygdala–nucleus accumbens pathway but with different time‐courses

Abstract

Excitatory glutamatergic fibers from limbic structures, such as the hippocampus and the basolateral amygdala, are known to converge on the same neurons in the nucleus accumbens. We have recently shown that ketamine, at a dose (25 mg/kg) that produces psychosis-like behaviors in rats, decreases glutamatergic transmission between the hippocampus and the nucleus accumbens. Here we investigated whether ketamine also affects glutamatergic transmission between the basolateral amygdala and the nucleus accumbens. We also studied the effects of amphetamine (1.5 mg/kg), known to evoke psychosis-like behaviors in rats. We found that each drug produced a long-lasting (at least 30 min) potentiation of synaptic efficacy in the projection from the basolateral amygdala to the nucleus accumbens. However, while this synaptic potentiation developed shortly after ketamine injection (within 4 min), it occurred after a 30-min delay in rats injected with amphetamine. These data reveal, in freely behaving rats, that ketamine has a more rapid and powerful effect on projection targets of the basolateral amygdala than does amphetamine.

Ketamine, at a Dose that Disrupts Motor Behavior and Latent Inhibition, Enhances Prefrontal Cortex Synaptic Efficacy and Glutamate Release in the Nucleus Accumbens

“…It is possible that glutamatergic mechanisms might also participate to the acquisition of latent inhibition. Dysfunction of glutamatergic inputs to the accumbens by ketamine (Hunt et al, 2005;Kessal et al, 2005 and present results) might therefore underlie the disruption of latent inhibition observed with this compound in our conditioned-fear paradigm.…”

Amphetamine Exposure Enhances Accumbal Responses to Reward-Predictive Stimuli in a Pavlovian Conditioned Approach Task

“…In contrast, systemic AMPH administration in behaving animals has more heterogeneous effects (Rebec, 1987;Haracz et al, 1993;Kessal et al, 2005). The present study showed that systemic AMPH administration in behaving animals can enhance particular excitatory task-related firing patterns, while leaving others unaffected.…”

Memory and psychostimulants: modulation of Pavlovian fear conditioning by amphetamine in C57BL/6 mice

“…An acute, low dose of amphetamine (1.5 mg/kg) has been shown to enhance synaptic transmission between the basolateral amygdala and nucleus accumbens, 30 min after the injection (Kessal et al 2005). Chronic, but not acute, doses of amphetamine (between 1 and 4 mg/kg) have been shown to induce an up-regulation of glial fibrillary acidic protein (GFAP), which is considered a marker of astrogliosis and neurotoxicity, in the rat hippocampus (Frey et al 2006).…”

“…The amygdala, and specifically the basolateral/lateral complex of the amygdala, is involved in encoding an aversive association with both the context and tone (Fanselow and Gale 2003;Fanselow and Poulos 2005). Amphetamine has been shown to alter amygdalar activity in a number of ways, including potentiating the synaptic transmission between the amygdala and nucleus accumbens (Kessal et al 2005). The hippocampus has also been implicated in amphetamine-induced locomotor activity, as lesions of the ventral hippocampus (VH) disrupt amphetamine-induced locomotion, and stimulation enhances it (White et al 2006).…”