UNCONTROLLABLE SHOCK INDUCES A BEHAVIORAL DEFICIT IN THE RAT SPINAL CORD: ROLE OF GABA. S.N.Washburn*; A.R.Ferguson; B.C.Patton; J.W.Grau. Dept Psychol, Texas A&M Univ, College Station, TX, USA
Exposure to an uncontrollable nociceptive stimulus undermines behavioral potential within the spinal cord. Evidence suggests that this behavioral deficit is linked to the induction of central sensitization. Both effects are blocked by pretreatment with an NMDA antagonist (MK-801: Ferguson et al., Society For Neuroscience Abstracts 2002). Paradoxically, both effects are also blocked by drugs that inhibit GABA function (e.g., the GABA-A antagonist, bicuculline), a manipulation that should enhance neural excitability. This suggests that manipulations that down-regulate neural excitability, by potentiating GABA-mediated inhibition, should not prevent the deficit and may emulate the adverse consequences of nociceptive stimulation. Experiment 1 examined whether an anesthetic dose of pentobarbital (which enhances GABA-mediated Cl conductance in the spinal cord) blocks the development of the deficit. Rats were transected at the second thoracic vertebra (T2) and 24 hrs later given i.p. saline or pentobarbital (40 mg/kg) followed by 6 min of uncontrollable shock. Behavioral potential was measured 24 hrs later by assessing the acquisition of a simple instrumental response. Pentobarbital did not prevent the negative consequences of uncontrollable nociceptive stimulation. Experiment 2 showed that the GABA-A agonist muscimol (given intrathecally) undermines learning in a dose-dependent fashion. Experiment 3 revealed that this inhibitory effect wanes within 24 hrs.
Supported by: MH60157 to JWG.
Citation: S.N.Washburn, A.R.Ferguson, B.C.Patton, J.W.Grau. UNCONTROLLABLE SHOCK INDUCES A BEHAVIORAL DEFICIT IN THE RAT SPINAL CORD: ROLE OF GABA. Program No. 166.6. 2002 Abstract Viewer/Itinerary Planner. Washington, DC: Society for Neuroscience, 2002. CD-ROM.