Latent inhibition (LI) is the attenuation in the acquisition of Pavlovian conditioning to a conditioned stimulus (CS) due to prior extensive exposure to that CS. It is assumed that LI is an animal model of attention in that animals learn to ignore the preexposed CS. The present series of experiments investigated the effects of selective serotonergic (5-HT) ligands known to increase 5-HT neurotransmission on LI using a conditioned emotional response (CER) procedure. In experiment 1, rats preexposed (PE) to 40 presentations of a tone CS acquired CER suppression more slowly than vehicle-treated nonpreexposed (NPE) animals, suggesting LI was obtained. Administration of 10 mg/kg fluoxetine (i.p.) did not influence CER acquisition in PE animals, suggesting that LI was not affected by fluoxetine. However, it was assumed that 40 CS presentations exerted a powerful LI effect, which might mask any effect of fluoxetine. Consequently, we assessed the effects of 5-HT ligands on LI following 10, rather than 40, CS preexposures. Under these conditions, both acute fluoxetine (experiment 2), and chronic (14 day) fluoxetine (experiment 3) administration, were found to augment LI. Experiment 4 suggested that acute administration of the 5-HT2 agonist DOI (2.5 mg/kg) also enhances LI. Experiment 5 revealed that 1 mg/kg 8-OH-DPAT did not influence LI, suggesting that postsynaptic 5-HT1a receptors are not involved in LI. These results suggest that enhancement of 5-HT neurotransmission enhance LI and that this effect is mediated, in part, through the 5-HT2 receptor subtype. The results are discussed within the context of the switching model of LI, which suggests that the effects of 5-HT are mediated through the modulation of the mesolimbic dopamine pathway.

The effects of repeated, once daily exposure to either tail pinch or restraint stress on extracellular DA levels in nucleus accumbens (NAcc), prefrontal cortex (PFC), and striatum (STR) was monitored in conscious rats using high-speed chronoamperometry, an electrochemical detection technique. The first exposure to either stress reliably and consistently elevated DA levels in the extracellular space of NAcc, PFC, and STR; the increases observed in PFC were of a greater magnitude than those observed in NAcc and STR. These data are consistent with those of previous studies suggesting a higher responsiveness of the meso-PFC system to stress. However, with repeated exposure increases in DA levels elicited by restraint became progressively larger in NAcc, and to a lesser extent also in STR, but not in PFC. Apomorphine, injected at autoreceptor selective doses, attenuated tail pinch and restraint stimulated increases in DA levels in NAcc but not in PFC, a finding consistent with the drug's action on impulse-modulating receptors of meso-NAcc DA neurons and with the known absense of such receptors on meso-PFC DA neurons. That DA was the primary contributor to the electrochemical signals was confirmed by the potentiating effect of GBR-12909, a selective DA uptake inhibitor, on restraint-elicited electrochemical responses in PFC and NAcc. / Taken together, the results of the present study indicate that with repeated exposure the meso-NAcc DA response to subsequent exposure to stress is enhanced. The data indicate that this pathway, which is thought to mediate the positive reinforcing effects of rewards, is also activated during behaviors motivated by aversive stimuli.

Differences in the activity of various components of the endogenous opioid system under basal conditions and following ethanol exposure have been reported between strains and lines of animals showing either a high or low ethanol consumption. The objective of the present studies was to investigate the presence of differences in (a) the density of kappa opioid binding sites, (b) the content of prodynorphin mRNA and (c) the content of dynorphin peptides in distinct brain regions between C57BL/6 (ethanol-preferring) and DBA/2 (ethanol avoiding) mice. Results indicated that the C57BL/6 mice have a higher content of kappa opioid binding sites and of dynorphin A 1--13 in the amygdala, and of dynorphin A 1--8 in the ventral tegmental area, while the DBA/2 mice presented a significantly hew content of kappa opioid binding sotes, prodynorphin mRNA as well as dynorphin A 1--13 and dynorphin A 1--8 peptides in the nucleus accumbens and septum. In addition, the DBA/2 mice presented a higher content of kappa opioid receptors in the periaqueductal grey and of dynorphin A 1--13 and dynorphin A 1--8 in the caudate putamen. Since the enhanced stimulation of kappa opioid receptors at the level of the nucleus accumbens has been associated with decreased dopamine release and aversive states, the higher content of kappa opioid receptors, prodynorphin mRNA and dynorphin peptides (the endogenous ligand of kappa binding sites), in regions of the limbic system of the DBA/2 mice may play an important role in determining their low alcohol consumption.

<p> Pupil dilation measures provide a useful index of test-taking processes. Prior research has established a simple positive relationship between pupil dilation magnitude and (i) threat levels, (ii) task difficulty levels, and (iii) working memory capacity. Surprisingly few studies have investigated the interaction of these three pupil response drivers. Do they add in a linear fashion, like separate weights on a single scale (as the "load" metaphor suggests), or is their relationship more complicated? To test of this question, I used a 2 X (2 X 3) mixed experimental design with random assignment to working memory resource depletion and nondepletion groups. These groups completed two versions of the same task, where response inhibition is required repeatedly in the depleting but is not required in the nondepleting version. Next, all subjects completed a test (90 factor-multiple judgment items) that employed two levels of difficulty (easy and difficult) and three levels of threat (safe, partially cued threat, and fully cued threat). Test-taking pupil data were collected at 60 Hz using a Tobii eye-tracker. Results indicated that levels of threat and task difficulty independently contribute to pupil response magnitude and they do not moderate one another. Apparently, the effects of difficulty and threat are not moderated by resource depletion; however, this study lacked power to detect anything less than a strong depletion effect. Results indicate that test-taking pupil responses are sensitive to testing conditions (e.g., threat and difficulty), but it remains unclear whether these responses are also sensitive to priming conditions (e.g., resource depletion).</p>

The neurobiological model of Post-Traumatic Stress Disorder, based upon the neurobiological model of fear-conditioning, states that the amygdala is hyperactivated, while other, inhibiting structures, like the Anterior Cingulate Cortex (ACC), are hypoactivated, therefore not fully inhibiting the amygdala. Two structural neuroimaging studies have examined the ACC volume to try to comprehend the hypoactivation of the ACC observed in subjects suffering from PTSD. Yamasue et al. (2003) found a lower grey matter density in the ACC of subjects with PTSD. Rauch et al. (2003) found a lower volume of the affective division of the ACC in subjects with PTSD compared to subjects exposed to trauma who did not suffer from PTSD. Comparing 14 subjects with Acute PTSD to 14 healthy control subjects, we replicated the results of Yamasue et al. (2003), but failed to observe any volumetric differences. Further analyses allowed us to be the first study to show that the nature of the difference observed in grey matter density was a shape difference of the ACC. Thus ACC volume does not seem to be related to Acute PTSD. Furthermore, this difference in shape raises questions as to the validity of the results of functional neuroimaging studies and of the neurobiological model of PTSD.

During the brief, high frequency, head rotations associated for example with the stepping jolts of normal locomotion, the vestibular semicircular canals accurately transduce instantaneous head angular velocity relative to space. However, during more prolonged rotations such as occur when walking along a curved pathway, the canal's biophysics lead to an exponential decay of the peripheral sensory signal with a human time constant on the order of 8 sec. Although this time constant is "neurally" augmented two or three fold in the brainstem, the decaying characteristic still incurs a progressively decreasing signal at this level in the CNS. The present study aimed to determine whether conscious human perception can correct for this form of error in the vestibular sensory signal. / Vestibular perception was estimated from a perception-based motor read out using two complimentary approaches. The first employed gaze saccades (either eyes alone or eye + head) to recapture a remembered target position after a passive head rotation of up to 8 sec, all conducted in complete darkness (Vestibular Memory Contingent Saccades = VMCS). The second study called for continuous "visual" fixation on an imagined earth-fixed target in the dark during the turn (Gaze Stabilization). In both studies final gaze error provided an index of volitional motor response accuracy. / The Results of both studies showed that final gaze position, and hence presumably vestibular perception, was on average not reduced from ideal (P $<$ 0.01, 21 subjects) over the full range of rotational durations. However, the Gaze Stabilization study showed that slow-phase velocity of the compensatory vestibulo-ocular reflex (VOR) followed the expected brainstem signal decay. But this response error tended to be systematically corrected by internally generated saccades. (Abstract shortened by UMI.)

Thesis (Ph.D.)--Pacific Graduate School of Psychology, 1989. / Source: Dissertation Abstracts International, Volume: 51-03, Section: B, page: 1494. Chairperson: Douglas Wallace.

Thesis (Ph.D.)--Pacific Graduate School of Psychology, 1998. / Source: Dissertation Abstracts International, Volume: 59-04, Section: B, page: 1906. Adviser: Teresa Elliott.

Thesis (Ph.D.)--Pacific Graduate School of Psychology, 1998. / Source: Dissertation Abstracts International, Volume: 59-10, Section: B, page: 5589. Adviser: Amy Wisniewski.

Thesis (Ph.D.)--Pacific Graduate School of Psychology, 2000. / Source: Dissertation Abstracts International, Volume: 61-09, Section: B, page: 5001. Adviser: David Mohr.