Heritable differences in the effects of amphetamine but not DOI on startle gating in albino and hooded outbred rat strains

• Published in: Pharmacology, biochemistry and behavior Vol. 75; no. 1; pp. 191 - 197
• Main Authors: Swerdlow, Neal R., Shoemaker, Jody M., Platten, Amanda, Pitcher, Leia, Goins, Jana, Crain, Sarah
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 01.04.2003; Elsevier Science
• Subjects: Amphetamine; Amphetamine - pharmacology; Amphetamines - pharmacology; Animals; Apomorphine; Apomorphine - pharmacology; Biological and medical sciences; Brain Chemistry - drug effects; Brain Chemistry - genetics; Central Nervous System Stimulants - pharmacology; DOI; Dopamine; Dopamine Agonists - pharmacology; Dopamine Uptake Inhibitors - pharmacology; Dose-Response Relationship, Drug; Female; Hallucinogens - pharmacology; Male; Medical sciences; Phenotype; Prepulse inhibition; Rats; Rats, Long-Evans; Rats, Sprague-Dawley; Reflex, Startle - drug effects; Reflex, Startle - genetics; Schizophrenia; Serotonin; Serotonin Receptor Agonists - pharmacology; Species Specificity; Startle; Strain; Amphetamine; Dopamine; Serotonin; Schizophrenia; Startle; Apomorphine; DOI; Prepulse inhibition; Strain
• ISSN: 0091-3057; 1873-5177
• DOI: 10.1016/S0091-3057(03)00078-9

Sensorimotor gating, measured by prepulse inhibition (PPI) of the startle reflex, is reduced in schizophrenia patients and in rats treated with dopamine (DA) agonists. Strain and substrain differences in the sensitivity to the PPI-disruptive effects of DA agonists may provide insight into the basis for human population differences in sensorimotor gating. We reported heritable differences in sensitivity to the PPI-disruptive effects of the D1/D2 agonist apomorphine (APO) in Harlan Sprague–Dawley (SDH) and Long–Evans (LEH) rats, offspring (F1) of an SDH×LEH cross, and subsequent offspring (N2) of an SDH×F1 cross. In this study, we assessed the neurochemical specificity of this heritable phenotype across parental SDH and LEH strains, and their F1 and N2 offspring, based on their sensitivity to the PPI-disruptive effects of the indirect DA agonist d-amphetamine (AMPH) and the 5HT2A agonist DOI. AMPH sensitivity followed a gradient of SDH>N2>F1>LEH, consistent with past findings with APO. DOI sensitivity did not differ across strains or generations. These findings demonstrate that the heritable phenotype in this model is not specific to a particular compound (APO), and reflects physiological differences in the DAergic, but not serotonergic, regulation of PPI.