Repeated administration of amphetamine induces sensitisation to its disruptive effect on prepulse inhibition in the rat

• Published in: Psychopharmacologia Vol. 135; no. 4; pp. 401 - 406
• Main Authors: ZHANG, J, ENGEL, J. A, SÖDERPALM, B, SVENSSON, L
• Format: Journal Article
• Language: English
• Published: Berlin Springer 01.02.1998; Springer Nature B.V
• Subjects: Acoustic Stimulation; administration & dosage; Adrenal Cortex Hormones; Adrenal Cortex Hormones - metabolism; Adrenalectomy; Adult and adolescent clinical studies; Amphetamine; Amphetamine - administration & dosage; Amphetamine - pharmacology; Amphetamines; Animals; Basic Medicine; Biological and medical sciences; Central Nervous System Depressants; Central Nervous System Depressants - pharmacology; Central Nervous System Stimulants; Central Nervous System Stimulants - administration & dosage; Central Nervous System Stimulants - pharmacology; Dopamine D2 receptors; drug effects; Farmakologi och toxikologi; Haloperidol; Haloperidol - pharmacology; Male; Medical sciences; Medicinska grundvetenskaper; Mental disorders; metabolism; Neurosciences; Neurovetenskaper; pharmacology; Pharmacology and Toxicology; Psychology. Psychoanalysis. Psychiatry; Psychopathology. Psychiatry; Psychoses; Rats; Rats, Sprague-Dawley; Receptor mechanisms; Reflex; Reflex, Startle - drug effects; Schizophrenia; Sprague-Dawley; Startle; Amphetamine derivatives; Rat; Rodentia; Schizophrenia; Startle reflex; Psychosis; Multiple dose; Dopaminergic transmission; Vertebrata; Mammalia; Animal; Adrenal hormone; Amfetamine; Sensitization; Inhibition
• ISSN: 0033-3158; 1432-2072
• DOI: 10.1007/s002130050528

Male Sprague-Dawley rats were repeatedly treated with amphetamine (AMP, 1 mg/kg, SC) at 3- day intervals for 15 days and tested for prepulse inhibition of acoustic startle after each treatment. This treatment regimen induced sensitisation in the animals as evidenced by a progressive increase in the disruptive effect of AMP on prepulse inhibition. Persistent changes in brain function was indicated, since an increase in disruptive effect was observed in sensitised animals also after a 22-day-long drug- and test-free period. The development of sensitisation was blocked by pretreatment with haloperidol (HPD, 0.1 mg/kg, SC), which suggests that sensitisation to the disruptive effect of AMP was dependent on dopamine (DA) D2 receptor activation. Furthermore, the development of sensitisation was blocked by adrenalectomy, which suggests that sensitisation was dependent also on circulating adrenal hormones. Increased DA-ergic activity has been implicated in the pathophysiology of schizophrenia and AMP-induced sensitisation to the neuronal functions that modulate prepulse inhibition may be an experimental model to investigate this hypothesis.