title: Acute cocaine induced deficits in cognitive performance in rhesus macaque monkeys treated with baclofen.
abstract: BACKGROUND
  Acute and/or chronic exposure to cocaine can affect cognitive performance, which may influence rate of recovery during treatment.
  
  
  OBJECTIVE
  Effects of the GABA-B receptor agonist baclofen were assessed for potency to reverse the negative influence of acute, pre-session, intravenous (IV) injection of cocaine on cognitive performance in Macaca mulatta nonhuman primates.
  
  
  METHODS
  Animals were trained to perform a modified delayed match to sample (DMS) task incorporating two types of trials with varying degrees of cognitive load that had different decision requirements in order to correctly utilize information retained over the delay interval. The effects of cocaine (0.2, 0.4, and 0.6 mg/kg, IV) alone and in combination with baclofen (0.29 and 0.40 mg/kg, IV) were examined with respect to sustained performance levels. Brain metabolic activity during performance of the task was assessed using PET imaged uptake of [(18) F]-fluorodeoxyglucose.
  
  
  RESULTS
  Acute cocaine injections produced a dose-dependent decline in DMS performance selective for trials of high cognitive load. The GABA-receptor agonist baclofen, co-administered with cocaine, reversed task performance back to nondrug (saline IV) control levels. Simultaneous assessment of PET-imaged brain metabolic activity in prefrontal cortex (PFC) showed alterations by cocaine compared to PFC metabolic activation in nondrug (saline, IV) control DMS sessions, but like performance, PFC activation was returned to control levels by baclofen (0.40 mg/kg, IV) injected with cocaine.
  
  
  CONCLUSIONS
  The results show that baclofen, administered at a relatively high dose, reversed the cognitive deficits produced by acute cocaine intoxication that may have implications for use in chronic drug exposure.
authors: Department of Physiology and Pharmacology, Wake Forest University Health Sciences, Winston-Salem, NC 27157, USA.
authors: Linda J
authors: LJ
authors: Porrino
authors: Robert E
authors: RE
authors: Hampson
authors: Ioan
authors: I
authors: Opris
authors: Samuel A
authors: SA
authors: Deadwyler
mesh_terms: D000818:Animals; D001418:Baclofen / Q000008:administration & dosage / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D003042:Cocaine / Q000008:administration & dosage / Q000633:toxicity*; D003071:Cognition / Q000187:drug effects; D003072:Cognition Disorders / Q000139:chemically induced / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D019788:Fluorodeoxyglucose F18; D058786:GABA-B Receptor Agonists / Q000008:administration & dosage / Q000494:pharmacology*; D007275:Injections, Intravenous; D008253:Macaca mulatta; D008297:Male; D049268:Positron-Emission Tomography / Q000379:methods; D017397:Prefrontal Cortex / Q000187:drug effects / Q000378:metabolism; D019275:Radiopharmaceuticals
chemical_list: D058786:GABA-B Receptor Agonists; D019275:Radiopharmaceuticals; D019788:Fluorodeoxyglucose F18; D001418:Baclofen; D003042:Cocaine