title: Amphetamine-modified acoustic startle responding and prepulse inhibition in adult and adolescent alcohol-preferring and -nonpreferring rats.
abstract: Selective breeding has been used to develop the alcohol-preferring (P) and -nonpreferring (NP) rats, with the P rat having lower CNS levels of dopamine (DA) and reduced DA innervation in the nucleus accumbens compared with the NP rat. The acoustic startle response (ASR) and prepulse inhibition (PPI) of the ASR are experimental behaviors altered by DA agonists. We examined whether functional differences in amphetamine (AMPH)-modified ASR and PPI exist between P and NP rats. AMPH [0.0 (saline), 1.0, 2.0, or 4.0 mg/kg] was injected 15 min prior to placement into a startle apparatus. After a 5-min habituation period, rats were given approximately twelve 95-, 105-, or 115-dB white-noise burst (ASR) and PPI trials. As adults, P rats were sensitive to AMPH potentiation of the ASR to a greater extent than NP rats. During adolescence, P and NP rats had similar levels of AMPH-potentiated ASR. As adults, NP rats displayed potentiated, rather than disrupted, PPI at the 1.0-mg/kg dose, whereas P rats displayed the expected disrupted PPI at the 4.0-mg/kg dose. As adolescents, NP rats did not display significant differences in PPI after AMPH, whereas P rats displayed dose-dependent disruption of PPI, which was significant at the 4.0-mg/kg dose. The limited effect of AMPH on increasing the ASR and the presence of AMPH-potentiated PPI at the lowest dose in the adult NP rat suggests reduced functioning of the interactions between DA circuits and the neurocircuitry mediating the ASR and PPI, compared with P rats. However, the neurocircuitry mediating PPI does not appear to be fully developed in the adolescent NP rat. The present findings also indicate that lower levels of DA content and immunoreactive fibers in the P rat may not reflect reduced DA neuronal activity, because the P rat displayed AMPH-potentiated ASR, and, at the highest dose, AMPH disruption of PPI during both adulthood and adolescence.
authors.affiliation: Institute of Psychiatric Research, Indiana University School of Medicine, 791 Union Drive, Indianapolis, IN 46202-4887, USA. ribell@iupui.edu
authors.forename: R L
authors.initials: RL
authors.lastname: Bell
authors.forename: Z A
authors.initials: ZA
authors.lastname: Rodd
authors.forename: C C
authors.initials: CC
authors.lastname: Hsu
authors.forename: L
authors.initials: L
authors.lastname: Lumeng
authors.forename: J M
authors.initials: JM
authors.lastname: Murphy
authors.forename: W J
authors.initials: WJ
authors.lastname: McBride
mesh_terms: D000161:Acoustic Stimulation; D000375:Aging / Q000523:psychology*; D000428:Alcohol Drinking / Q000235:genetics* / Q000523:psychology*; D000661:Amphetamine / Q000494:pharmacology*; D000818:Animals; D000697:Central Nervous System Stimulants / Q000494:pharmacology*; D004298:Dopamine / Q000502:physiology; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D051381:Rats; D013216:Reflex, Startle / Q000187:drug effects*
chemical_list: D000697:Central Nervous System Stimulants; D018765:Dopamine Uptake Inhibitors; D000661:Amphetamine; D004298:Dopamine