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The rostral anterior cingulate cortex (rACC) is involved in supraspinal nociceptive processing. ACC lesions relieve persistent pain, but do not affect the patient's ability to localize a noxious stimulus. Since the rACC has a high density of GABA receptors, it is possible that pain processing is influenced by these receptors in the rACC. The present experiments examined the involvement of rat rACC GABA(A) and GABA(B) receptors in regard to sensitivity to mechanical stimulation and escape/avoidance behavior in response to a noxious stimulus following L5 spinal nerve ligation. Rats were or were not afflicted with a neuropathic pain condition by an L5 spinal nerve ligation. rACC microinjection of 10 microg/microl GABA, a GABA(A) agonist (0.001 microg/microl, 0.1 microg/microl, or 0.5 microg/microl muscimol), a GABA(B) agonist (0.1 microg/microl, 1 microg/microl, or 5 microg/microl baclofen), or saline, did not alter mechanical withdrawal thresholds. Importantly, following 10 microg/microl GABA, 0.1 microg/microl, or 0.5 microg/microl muscimol microinjected into the rACC, place escape/avoidance behavior to a noxious mechanical stimulus was attenuated in injured animals. The attenuation was specific to the rACC and was blocked by a preadministered microinjection of the appropriate antagonist(s) into the rACC. In conclusion, microinjection of GABA and higher doses of muscimol did not decrease mechanical hyperalgesia but did attenuate place escape/avoidance behavior that is associated with mechanical stimulation of the ligated paw. These results provide additional support for the role of the rACC in higher order supraspinal processing of noxious events and suggest that rACC GABA(A) receptors significantly contribute to this processing.

These experiments examined the involvement of cholinergic influences in the effects of GABAergic drugs on 24-h retention of an inhibitory avoidance response by mice. A first set of experiments confirmed previous findings indicating that post-training injections (ip) of the GABAergic agonists muscimol (1.0 and 2.0 mg/kg) and baclofen (10.0 and 20.0 mg/kg) impaired retention, as well as previous findings indicating that injections of the cholinergic agonist oxotremorine (5.0 and 10.0 micrograms/kg) enhanced retention. The findings of a second set of experiments indicated that the memory-impairing effects of muscimol and baclofen were attenuated by concurrent injections of a low, and otherwise ineffective, dose of oxotremorine (2.5 micrograms/kg). These findings are interpreted as suggesting that GABAergic drugs affect memory storage through influences on cholinergic systems.