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Item Developmental differences in hypothermic and behavioral responses to ethanol treatment in Alcohol Preferring and Non-Preferring Rats(2012-08-30) Myers, Mallory Lynn; Goodlett, Charles R.; Murphy, James M.; Bell, Richard L.Differences in voluntary consumption of ethanol have been negatively correlated with differences in initial sensitivity and tolerance to ethanol’s pharmacological effects. From this perspective, both adolescent and adult alcohol-nonpreferring (NP) rats would be expected to be initially more sensitive to the sedative and hypothermic effects of ethanol and fail to acquire tolerance to those effects than preferring (P) rats. The first objective of this experiment was to assess alcohol-induced hypothermia and locomotor sedation in adolescent and adult P and NP rats over five consecutive daily administrations (saline, 1.5 g/kg, or 3.0 g/kg ethanol 17%v/v), testing the hypothesis that the P rats would acquire tolerance to the hypothermic response whereas the NP rats would not show changes across days. In addition, it was hypothesized that there would be age-related differences in initial sensitivity to ethanol, evident by adolescent rats displaying less ethanol-induced hypothermia and locomotor sedation than adult rats on Day 1. The second objective was to determine if conditioning was occurring between the administration environment and the hypothermic response and locomotor sedation elicited by ethanol exposure, via a sixth injection of saline. Female rats were surgically implanted with intraperitoneal Mini Mitter telemetry probes on postnatal day 25 or 85 and experimental manipulations began five days later. Data were collected every minute; temperature data were then converted to change from baseline scores and locomotor data were totaled for each session. On Day 1, maximum temperature reduction elicited by the 3.0 g/kg dose was greater in the NP rats than the P rats, regardless of age. That dose also produced greater levels of locomotor sedation in the adult rats compared to the adolescent rats, regardless of line. The 1.5 g/kg dose of ethanol produced a greater hypothermic response in adult rats compared to adolescent rats, locomotor activity was reduced equally across the groups. With repeated administrations, NP adult rats displayed sensitization to the hypothermic response elicited from the 3.0 g/kg dose; in contrast, tolerance to the hypothermic response was found within the 1.5 g/kg dose for the adolescent P, adult P, and the adult NP rats. Repeated saline administrations also resulted in tolerance to the hypothermic response associated with administration in the adult NP and adolescent P rats. On the Day 6 saline administrations, adult rats which had previously been exposed to the 3.0 g/kg dose, maintained their baseline body temperatures better than both of the other exposure groups. Adolescent rats failed to show any signs of conditioning when administered saline on Day 6. Contrary to prediction the P rats failed to acquire tolerance to the 3.0 g/kg dose for either measure; and the line difference in ethanol-induce hypothermia was due to sensitization of the hypothermic response in adult NP rats. These results also provide further support that adolescent rats are less sensitive to the initial aversive effects of ethanol at the 1.5 g/kg dose for ethanol-induced hypothermia and the 3.0 g/kg dose for locomotor activity. The current experiment provides evidence that initial sensitivity as well as the acquisition of tolerance to ethanol-induced hypothermia may be behavioral phenotypes correlated with selection for high and low alcohol drinking preference.Item Increased delay discounting tracks with later ethanol seeking but not consumption(2014-07-31) Beckwith, Steven Wesley; Czachowski, Cristine; Grahame, Nicholas J.; Lapish, ChristopherAssessments of delay discounting in rodent lines bidirectionally selected for home cage intake and preference of alcohol have had mixed findings. The current study sought to examine if delay discounting related differentially to alcohol seeking versus and alcohol drinking, two processes underlying alcohol intake and preference. Three strains of rats were utilized to answer this question Long Evans (LE), high alcohol drinking rats (HAD2), and alcohol preferring P rats. All strains were compared in an adjusting amount delay discounting task. Operant self-administration of alcohol was then assessed in the sipper tube model, and finally home cage drinking was assessed in a 24 hour 2 bottle choice paradigm. In the delay discounting it was found that the P rats were steeper discounters than both the LE and HAD2. In the sipper tube model, P rats displayed higher levels of seeking than both the HAD2s and the LE, but both the P rats and the HAD2s had higher intakes than the LE. During 24 hour home cage access, the P rats and the HAD2s had higher intake and preference for alcohol than the LE, but were not different from each other. These results show that increased discounting of delayed rewards tracks with appetitive processes versus consummatory factors and home cage intake of alcohol. This builds on prior findings using selected line pairs by providing an explanation for discordant results, and supports the hypotheses that increased delay discounting is an intermediate phenotype that predisposes individuals to alcohol use disorders.Item The Psychobiology of Conscience(2009) IU Conscience ProjectItem Temporally distinct impairments in cognitive function following a sensitizing regimen of methamphetamine(2014-08-01) Janetsian, Sarine Sona; Lapish, Christopher; Neal-Beliveau, Bethany S.; Goodlett, Charles R.Methamphetamine (MA) is a widely abused psychostimulant that has been shown to evoke an array of neurobiological abnormalities and cognitive deficits in humans and in rodent models (Marshall & O'Dell, 2012). Alterations in cognitive function after repeated drug use may lead to impaired decision-making, a lack of behavioral control, and ultimately the inability to abstain from drug use. Human studies have shown that alterations in neurobiology resulting from prolonged MA use may lead to a number of cognitive deficits, including impairments in executive function, learning, memory, and impulsivity. These impairments, specifically those that engage the prefrontal cortex (PFC) or hippocampus (HC), may persist or recover based on the duration of abstinence. In rodents, repeated intermittent injections of MA yield protracted changes in neurobiology and behavior, which have been shown to effectively model a number of the biological and cognitive abnormalities observed in addiction. In order to assess the temporal evolution of impaired cognitive function throughout abstinence, sensitization was first induced in rats (7 x 5.0 mg/kg MA over 14 days). MA-treated rats initially exhibited a robust increase in locomotion that transitioned to stereotypy as the induction phase progressed. Then, the effects of MA sensitization on social interaction (SI), temporal order recognition (TOR) and novel object recognition (NOR) was assessed at one-day and 30-days post induction. No differences were observed in SI in either group or after a single injection of MA. However, an acute injection of 5.0 mg/kg of MA 30-minutes prior to testing dramatically reduced SI time. Impairments in TOR and NOR were observed in MA-treated rats after one day of abstinence, and impairments in TOR, but not NOR, were observed on day 30 of abstinence. No differences in TOR and NOR after a single injection of MA or saline were observed. These data establish that after 30 days of abstinence from a sensitizing regimen of MA, the ability to recall the temporal sequence that two stimuli were encountered was impaired and that was not attributable to impaired novelty detection. These data also suggest that at least some of the neurocognitive abnormalities caused by chronic MA administration may normalize after prolonged abstinence, since the ability to detect novelty recovered after 30 days of abstinence. These data provide compelling support that, since MA-sensitization caused temporal deficits in memory, PFC and HC function may be differentially impaired throughout the time course of abstinence.