Effects of caffeine on sensorimotor gating of the startle reflex in normal control subjects: impact of caffeine intake and withdrawal

Abstract. Rationale: Prepulse inhibition (PPI), a cross–species measure of sensorimotor gating, is impaired in certain neuropsychiatric disorders. This study was designed to assess caffeine effects on PPI in normal humans, as part of an effort to understand cross-species differences and similarities in the neurochemical regulation of PPI. Methods: Startle was measured during a screening session; 7 days later, subjects were retested after placebo or caffeine (200 mg; double-blind design). Subjects were characterized as low versus high caffeine drinkers based on established scales (range 11–628 mg/day), and either maintained ad libitum caffeine intake (Ad lib study; n=18) or refrained from caffeine consumption for ≥15 h prior to testing (Withdrawal study; n=12). Autonomic and self-rating measures, acoustic and tactile startle, and unimodal and cross-modal PPI, were measured in divided sessions for 3 h post-treatment. Results: There were significant effects of caffeine and/or caffeine withdrawal on several self-rating and autonomic measures, and on startle reflex habituation, but not on acoustic or tactile startle magnitude or PPI. Difference scores of startle data from screening versus test days revealed no group effects on startle magnitude, but PPI difference scores revealed that caffeine had opposite effects on low versus high caffeine drinkers (means=57 versus 258 mg/day) in the two withdrawal states. In the absence of withdrawal, caffeine reduced PPI in heavy caffeine drinkers; during withdrawal, caffeine increased PPI in heavy caffeine drinkers. The opposite pattern was evident in low caffeine drinkers. Conclusions: While a physiologically active dose of caffeine has no simple effects on PPI in normal humans, both withdrawal states and normal levels of caffeine consumption may be important factors in understanding this drug's effects on sensorimotor gating.

[1]  N. Swerdlow,et al.  Changes in sensorimotor inhibition across the menstrual cycle: Implications for neuropsychiatric disorders , 1997, Biological Psychiatry.

[2]  C. Grillon,et al.  Startle gating deficits occur across prepulse intensities in schizophrenic patients , 1992, Biological Psychiatry.

[3]  M. Geyer,et al.  Impaired startle prepulse inhibition and habituation in patients with schizotypal personality disorder. , 1993, The American journal of psychiatry.

[4]  A. Mcghie,et al.  Disorders of attention and perception in early schizophrenia. , 1961, The British journal of medical psychology.

[5]  S. Hackley,et al.  The more or less startling effects of weak prestimulation - Revisted : Prepulse modulation of multicomponent blink reflexes , 1997 .

[6]  A. Paterson,et al.  Dopamine D4 Receptor Gene: Novelty or Nonsense? , 1999, Neuropsychopharmacology.

[7]  E. Daneluzzo,et al.  Sensorimotor gating and habituation evoked by electro-cutaneous stimulation in schizophrenia , 1994, Biological Psychiatry.

[8]  H. Peak.  Time order error in successive judgments and in reflexes. I. Inhibition of the judgment and the reflex , 1939 .

[9]  G Burnstock,et al.  Nomenclature and Classification of Purinoceptors* , 2005 .

[10]  M. Geyer,et al.  Prestimulus effects on human startle reflex in normals and schizophrenics. , 1978, Psychophysiology.

[11]  N. Swerdlow,et al.  Neurophysiology and Neuropharmacology of Short Lead Interval Startle Modification , 1999 .

[12]  T. Blumenthal,et al.  Caffeine delays habituation of the human acoustic startle reflex , 1994, Psychobiology.

[13]  T. Blumenthal,et al.  The effects of different doses of caffeine on habituation of the human acoustic startle reflex , 1995, Pharmacology Biochemistry and Behavior.

[14]  A. Bond,et al.  The use of analogue scales in rating subjective feelings , 1974 .

[15]  H. Norris.  The action of sedatives on brain stem oculomotor systems in man. , 1971, Neuropharmacology.

[16]  K. Hutchison,et al.  Effect of d-amphetamine on prepulse inhibition of the startle reflex in humans , 1999, Psychopharmacology.

[17]  M. Dawson,et al.  Attentional modulation of short- and long-lead-interval modification of the acoustic startle eyeblink response: comparing auditory and visual prestimuli. , 1999, International journal of psychophysiology : official journal of the International Organization of Psychophysiology.

[18]  T. Blumenthal,et al.  A relationship between inhibition of the acoustic startle response and the protection of prepulse processing , 1996, Psychobiology.

[19]  N. Swerdlow,et al.  A comparison of the effects of amphetamine, strychnine and caffeine on prepulse inhibition and latent inhibition , 1995, Behavioural pharmacology.

[20]  M A Geyer,et al.  Using an animal model of deficient sensorimotor gating to study the pathophysiology and new treatments of schizophrenia. , 1998, Schizophrenia bulletin.

[21]  K. Hutchison,et al.  Personality factors moderate subjective and psychophysiological responses to d-amphetamine in humans. , 1999, Experimental and clinical psychopharmacology.

[22]  M. Koch,et al.  The acoustic startle response in rats—circuits mediating evocation, inhibition and potentiation , 1997, Behavioural Brain Research.

[23]  R. Kahn,et al.  The effects of low dose ketamine on sensory gating, neuroendocrine secretion and behavior in healthy human subjects , 1998, Psychopharmacology.

[24]  M. Geyer,et al.  Opposite effects of 3,4-methylenedioxymethamphetamine (MDMA) on sensorimotor gating in rats versus healthy humans , 1999, Psychopharmacology.

[25]  N. Swerdlow,et al.  Towards a cross-species pharmacology of sensorimotor gating: effects of amantadine, bromocriptine, pergolide and ropinirole on prepulse inhibition of acoustic startle in rats , 1998, Behavioural pharmacology.

[26]  M. Flaten,et al.  Caffeine and prepulse inhibition of the acoustic startle reflex , 1999, Psychopharmacology.

[27]  N. Swerdlow,et al.  Cross‐species Studies of Sensorimotor Gating of the Startle Reflex , 1999, Annals of the New York Academy of Sciences.

[28]  B. Toone,et al.  The effect of apomorphine and L-dopa challenge on prepulse inhibition in patients with parkinsons disease , 1995, Schizophrenia Research.

[29]  T. Sharma,et al.  Normalization of information processing deficits in schizophrenia with clozapine. , 1999, The American journal of psychiatry.

[30]  Regulation of sensorimotor gating by interactions of dopamine and adenosine in the rat , 1998, Behavioural pharmacology.

[31]  Jeffrey A. Gray,et al.  Effect of cigarette smoking on prepulse inhibition of the acoustic startle reflex in healthy male smokers , 1996, Psychopharmacology.

[32]  N. Swerdlow,et al.  The neural substrates of sensorimotor gating of the startle reflex: a review of recent findings and their implications , 1992, Journal of psychopharmacology.