Life Sciences, Vol. 39, pp. 1667-1674 Pergamon Journal~ Printed in the U.S.A. NOCICEPTIVE RESPONSES TO ALTERED GABAERGIC ACTIVITY AT THE SPINAL CORD Lowell A. Roberts, Carlos Beyer and Barry R. Komisaruk Institute of Animal Behavior Rutgers University i01 Warren Street Newark, NJ, 07102 (Received in final form August 5, 1986) Summary GABA agonists and antagonists were injected intrathecally at the spinal cord, to determine their effect on nocicep- tive thresholds. Tactile stimulation, applied against the flank by a medium diameter von Frey fiber (5.5 g force), elicited distress vocalizations after, but not before injection of the GABA antagonists, bicuculline MI or picro- toxin (0.25 and 1 Dg dosages). Vocalization threshold to tail shock was significantly reduced by bicuculline MI or picrotoxin. Tail flick withdrawal latency from radiant heat was not altered by GABA antagonists. The GABA agonist, muscimol, significantly elevated vocalization threshold to tail shock at a 5 ug dose. At a lower dose level (i ug), muscimol significantly reduced vocalization threshold to tail shock. Tail flick latency was significantly prolonged by the 5 ug dose of muscimol; however, flaccid paralysis of the hind limbs was also evident. Nociceptive thresholds were not altered by GABA or saline injection. These findings indicate that GABAergic activity contributes to the tonic modulation of nociception at the spinal cord. Stimulation of GABAergic activity by GABA agonists, uptake inhibitors, or transaminase inhibitors, promotes analgesia (1-4). In contrast, GABA antagonists are convulsive agents, provoking clonic and locomotor seizures when administered at spinal and supraspinal sites (5-6). Changes in pain perception in response to GABA antagonists would suggest a physiological role for GABA in pain modulation, but their effect on nociceptive responses has only recently been examined (7). Two types of GABA receptors have been characterized in the CNS. GABA "A" receptors are distinguished by the competitive antagonist bicuculline methiodide (BMI), and are activated by the specific agonist, muscimol (8-11). The non-competitive GABA antagonist, picrotoxin (PTX), suppresses activity in GABA-A mediated systems by directly blocking associated chloride ionophores (8-12). In contrast, GABA "B" receptors are not antagonized by bicuculline or other GABA-A antagonists, but are activated by the agonist baclofen (8-9,13). Unfortunately, a specific antagonist for GABA-B receptors is not currently available. 0024-3205/86 $3.00 + .00 Copyright (c) 1986 Pergamon Journals Ltd.