PubMed · 10738383
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D B Campbell, B J Anderson. 1999. Setting behavioral limits.. https://pubmed.ncbi.nlm.nih.gov/10738383/
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Phenytoin is a widely used anticonvulsant drug that also reduces aggressive behavior. Aggression in humans and animals is often associated with low serotonin levels. This study examined the anti-aggressive properties of phenytoin in rodent isolation-induced aggression using a resident-intruder test to quantify aggression. Chronic treatment with p-chlorophenyl-alanine (PCPA), a competitive inhibitor of serotonin synthesis, significantly enhanced resident attack behavior compared to saline-treated control rats. Phenytoin dose-dependently reduced aggressive behavior specifically in PCPA-treated rats, but had no anti-aggressive properties in saline-treated rats. These data suggest that aggressive behavior in this model may be related to neuronal hyperexcitability that is sensitive to the anticonvulsant effects of phenytoin. Further, these data suggest isolation-induced aggression in PCPA-treated rats may be a useful model to investigate aggression associated with low serotonin in the brain.
This study examined localization of positive versus negative motivational functions mediated by GABA circuits within the accumbens shell. Microinjections of a GABA(A) agonist (0, 25, 75, and 225 ng/0.5 microl muscimol) in rostral shell sites elicited appetitive increases in eating behavior. In contrast, microinjections in caudal shell sites elicited defensive burying or paw-treading behavior. Rats whose microinjections landed bilaterally outside of the accumbens shell did not display either behavior. Defensive treading elicited by caudal shell muscimol microinjection appeared to be a negative motivated response to threat (similar in parameters and orientation to normal defensive burying of a threatening electrified shock prod). The nucleus accumbens shell thus appears functionally heterogeneous in coding motivational valence. The demonstration that muscimol elicits positive eating behavior from rostral shell versus negative defensive behavior from caudal shell suggests in particular that GABAergic substrates of positive and negative types of motivated behavior in the nucleus accumbens shell are segregated along a rostrocaudal gradient.