Reduced startle habituation and prepulse inhibition in mice lacking the adenosine A2A receptor.
Adenosine and dopamine receptors interact in the CNS to modulate behaviour, including sensorimotor gating. Prepulse inhibition (PPI) has been suggested to be an operational measure of sensorimotor gating. PPI and startle habituation are disrupted in patients with schizophrenia. In experimental animals, both parameters are modulated by dopaminergic and adenosine receptor agonists and antagonists. In the present study, we measured PPI and startle habituation in mice that lack functional adenosine A(2A) receptors. Startle amplitudes, startle habituation and PPI were significantly reduced in mice homozygous null for the adenosine A(2A) receptor (A(2A)(-/-)). In addition, differential effects of amphetamine and MK-801 on startle amplitude, startle habituation and PPI were observed between A(2A)(-/-) and wildtype controls. These data support the involvement of adenosine A(2A) receptors in regulation of PPI and startle habituation.
Wang
Jian Hong
JH
Behavioural Neuroscience Laboratory, Mental Health Research Institute of Victoria, 155 Oak street, Parkville, Vic., Australia.
Short
Jennifer
J
Ledent
Catherine
C
Lawrence
Andrew J
AJ
van den Buuse
Maarten
M
D000161:Acoustic Stimulation; D000661:Amphetamine / Q000494:pharmacology; D000818:Animals; D016291:Dizocilpine Maleate / Q000494:pharmacology; D015259:Dopamine Agents / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D006185:Habituation, Psychophysiologic / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009433:Neural Inhibition / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D043705:Receptor, Adenosine A2A; D018047:Receptors, Purinergic P1 / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D013216:Reflex, Startle / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D012684:Sensory Thresholds / Q000187:drug effects / Q000502:physiology*
D015259:Dopamine Agents; D018691:Excitatory Amino Acid Antagonists; D043705:Receptor, Adenosine A2A; D018047:Receptors, Purinergic P1; D016291:Dizocilpine Maleate; D000661:Amphetamine