Central and peripheral inflammatory responses associated with caffeine and cocaine administration in mice

BETINA GONZALEZ; FRANCISCO URBANO; JEAN LUD CADET; VERONICA BISAGNO; JAVIER A. MUÑIZ; EDGAR GARCIA-RILL

San Diego

Congreso; Neuroscience 2016; 2016

Society for Neuroscience

Cocaine is often used in combination with other psychostimulants like caffeine. Caffeine is also a common adulterant of seized regular cocaine samples or samples of ?coca paste? (an inexpensive by-product of processing raw coca leaf into cocaine). Thus, this study was aimed to investigate potential toxic effects of combined intake of caffeine and cocaine in mice. Male C57/BL-6 mice were treated with Cocaine-Coc- (10 mg/kg), Caffeine -Caf- (5mg/kg), their combination (Caf-Coc) (10 mg/kg Coc + 5 mg/kg Caf) or vehicle (Veh), in an intermittent binge protocol (3 i.p. injections, 1 h apart, one day on/off for 13 days). We investigated astroglial activation (by GFAP immunostaining) in some areas of the CNS (Ventral and Dorsal Striatum and Motor Cortex, M1) that are involved in reward and motor functions. In addition, we performed histopathological analysis on several organs: lung, heart, liver and kidney tissues (by H&E stain). Histopathological examinations (from tissue extracted 24 hours after chronic treatments) showed increased liver inflammation (hepatitis and/or hepatosis) in all psychostimulant-treated groups, however the group that received the combination of Caf-Coc was the only group that presented severe hepatitis and necrosis. Caf or Coc treatments used in this study did not induce signs of histopathology or inflammation in any of the other organs tested.Astrocytes are major contributors to synaptic plasticity induced by drugs of abuse and can react to various insults rapidly, leading to astrogliosis. In the present study, Coc, Caf and Caf-Coc groups showed significantly higher count of GFAP-positive astrocytes in the Dorsal Striatum (compared to Veh values) and the group that received both psychostimulants combined showed significantly higher number of GFAP-astrocytes compared to any other group. This effect decreased after a withdrawal period of seven days. We are currently measuring astrogliosis on the Ventral Striatum or M1 to clarify if increments in activated astroglia mediated by psychostimulants are area-dependent or part of a generalized inflammatory response.While caffeine have shown neuroprotective properties in neurotoxin models of Parkinson?s Disease, we did not find any protective effect induced by caffeine on cocaine-mediated alterations either at the CNS or peripherally. Moreover, our findings involving low intermittent caffeine doses suggest additive inflammatory responses of cocaine and caffeine on CNS and peripheral organs.