RATIONALE: The intake of psychostimulant drugs may induce cognitive dysfunction and negative affective-like states, and is associated with increased activity of stress-responsive systems. The corticotropin-releasing factor (CRF) system mediates neuroendocrine, behavioural and autonomic responses to stressors, and might be implicated in substance-related disorders. CRF signalling is mediated by two receptor types, named CRF1 and CRF2. OBJECTIVES: The present study aims to elucidate the role for the CRF1 receptor in cognitive dysfunction and anxiety-like states induced by cocaine. RESULTS: The genetic inactivation of the CRF1 receptor (CRF1+/- and CRF1-/-) does not influence recognition memory in drug-naïve mice, as assessed by the novel object recognition (NOR) test. Moreover, the chronic administration of escalating doses of cocaine (5-20 mg/kg, i.p.) induces NOR deficits, which are unaffected by CRF1 receptor-deficiency. However, the same drug regimen reveals an anxiety-like vulnerability to cocaine in CRF1-/- but not in wild-type or CRF1+/- mice, as assessed by the elevated plus maze test. CONCLUSIONS: The present findings indicate dissociation of cognitive dysfunction and anxiety-like states induced by cocaine. Moreover, they unravel a novel mechanism of vulnerability to psychostimulant drugs.
RATIONALE: The intake of psychostimulant drugs may induce cognitive dysfunction and negative affective-like states, and is associated with increased activity of stress-responsive systems. The corticotropin-releasing factor (CRF) system mediates neuroendocrine, behavioural and autonomic responses to stressors, and might be implicated in substance-related disorders. CRF signalling is mediated by two receptor types, named CRF1 and CRF2. OBJECTIVES: The present study aims to elucidate the role for the CRF1 receptor in cognitive dysfunction and anxiety-like states induced by cocaine. RESULTS: The genetic inactivation of the CRF1 receptor (CRF1+/- and CRF1-/-) does not influence recognition memory in drug-naïve mice, as assessed by the novel object recognition (NOR) test. Moreover, the chronic administration of escalating doses of cocaine (5-20 mg/kg, i.p.) induces NOR deficits, which are unaffected by CRF1 receptor-deficiency. However, the same drug regimen reveals an anxiety-like vulnerability to cocaine in CRF1-/- but not in wild-type or CRF1+/- mice, as assessed by the elevated plus maze test. CONCLUSIONS: The present findings indicate dissociation of cognitive dysfunction and anxiety-like states induced by cocaine. Moreover, they unravel a novel mechanism of vulnerability to psychostimulant drugs.
Authors: Richard L Hauger; Dimitri E Grigoriadis; Mary F Dallman; Paul M Plotsky; Wylie W Vale; Frank M Dautzenberg Journal: Pharmacol Rev Date: 2003-03 Impact factor: 25.468
Authors: S C Heinrichs; M P Stenzel-Poore; L H Gold; E Battenberg; F E Bloom; G F Koob; W W Vale; E M Pich Journal: Neuroscience Date: 1996-09 Impact factor: 3.590
Authors: G W Smith; J M Aubry; F Dellu; A Contarino; L M Bilezikjian; L H Gold; R Chen; Y Marchuk; C Hauser; C A Bentley; P E Sawchenko; G F Koob; W Vale; K F Lee Journal: Neuron Date: 1998-06 Impact factor: 17.173