Gordon K. Hodge

Long-term monoamine depletion, differential recovery, and subtle behavioral impairment following methamphetamine-Induced neurotoxicity

Squads of rats were assayed at three intervals following MA-induced neurotoxicity to investigate the persistence of monoamine deficits, the potential for monoamine recovery, and spatial task abilities. At 48, 139, and 237 days postinjection, MA animals showed significant monoamine depletions compared with controls. Investigating percent depletions (MA/control) across time showed monoamine recovery in some structures. Initially, 5-HT within medial prefrontal cortex (MPFC), caudate (CdN), and hippocampus (HPC) was reduced to 30% of control levels. By 237 days, MPFC and CdN levels were elevated to 70%. Similarly, initial CdN DA reductions (30% of control levels) showed recovery to 80% by 237 days. These findings support neurochemical recovery following MA neurotoxicity. However, the persistent depression of HPC 5-HT suggests that not all structures recover equally. The HPC did show elevated turnover (metabolite/neurotransmitter) over time, suggesting a unique compensatory response. MA treatment also produced an impairment in the Morris water-maze place task at 65 days postinjection. No impairments were observed in water-maze moving platform or place task at 79 and 165 days postinjection, respectively, or in T-maze alternation. The possibility that partial recovery in tissue monamine levels underlies the sparing of function and behavioral improvement is discussed.

Pars compacta of the substantia nigra modulates motor activity but is not involved importantly in regulating food and water intake

SummaryPrecise, bilateral radio-frequency lesions of pars compacta of the substantia nigra in rats resulted in the immediate and sustained appearance of hyperactivity, but such lesions did not produce significant alterations in food or water intake. These behavioral effects were correlated with considerable, histochemically assessed loss of dopamine terminals in the caudate-putamen complex, but dopamine innervation in nucleus accumbens and other forebrain areas was only slightly affected. The magnitude of motor activity increase was positively correlated with the degree of pars compacta involvement. Animals with lesions in the median raphe and adjacent reticular formation also displayed chronic hyperactivity. In contrast to rats receiving discrete radio-frequency lesions of pars compacta, animals with bilateral mesencephalic ablations produced by 6-hydroxydopamine (6-OHDA, 8 μg/4 μl or 4 μg/2 μl in combination with desipramine pretreatment) displayed poverty of movement. Furthermore, significant, dose-dependent decrements in food and water intake were seen after 6-OHDA. The nonselective component of such lesions was frequently large and irregular in shape. Occasional ablations produced by this neurotoxin, however, appeared more selective in that damage was confined primarily to pars compacta. Nonetheless, the best correlate of aphagia and adipsia associated with 6-OHDA treatment was lesion size, regardless of the extent of pars compacta or other nigral involvement. We conclude that aphagia and adipsia concomitant to 6-OHDA lesions of the substantia nigra result from the incidental destruction of extra-nigral systems. Virtually complete, but precise, lesions of pars compacta do not produce aphagia and adipsia. While our results are consistent with the notion that the substantia nigra serves an important role in the regulation of motor activity, they provide no support for the conjecture that it is importantly involved in mediating ingestive behaviors.

Simple and configural association learning in rats with bilateral quisqualic acid lesions of the nucleus basalis magnocellularis

We hypothesized that bilateral quisqualic acid lesions of the nucleus basalis magnocellularis (NBM) in rats would impair configural but not simple association learning. In experiment 1, rats were tested in a negative patterning operant discrimination where they were food-reinforced for responding to a light or a tone (L+, T+) but not for responding to the configural stimulus consisting of the light and tone presented simultaneously (LT-). Consistent with our hypothesis, NBM-lesioned rats showed a transient but significant impairment, responding normally to L+ and T+ but responding more often to LT-, in addition to responding more often during the inter-trial interval (ITI) than controls. In experiment 2, rats were tested in a simple operant discrimination where rats were food-reinforced for responding to a light (L+) but not for responding to a tone (T-). Although NBM-lesioned rats again responded normally to L+ as predicted, NBM-lesioned rats were transiently impaired, making more T- responses and more ITI responses than controls. Together, these results suggest that the NBM is involved in both configural and simple association learning but that this involvement is limited to learning to withhold responding to non-reinforced contextual or discrete stimuli. Finally, rats from experiment 2 underwent extinction trials, where results showed no difference between NBM-lesioned and control groups, suggesting that the NBM is not involved in the extinction of conditioned responding to previously reinforced stimuli.

Acquisition, retention, and extinction of operant discriminations in rats with nucleus basalis magnocellularis lesions.

Effects of bilateral ibotenic acid lesions of nucleus basalis magnocellularis (NBM) and scopolamine treatment on different aspects of learning and memory in an operant discrimination task were assessed. In Experiment 1, NBM lesions impaired acquisition performance. In Experiment 2, scopolamine lowered response rates but did not affect discrimination accuracy in lesioned or control rats. In Experiment 3, although pretrained rats showed transient increases in commission errors, percentage correct responding remained above chance levels after lesion. During extinction in Experiment 4, operant responding diminished more quickly in pretrained NBM-lesioned rats than in controls, but subsequent reacquisition performance was equivalent in both groups. Results suggest the NBM is importantly involved in discrimination learning, but cholinergic activity may be less critical for memory retention than for acquisition.

Use of a supplementary internet based education program improves sleep literacy in college psychology students

INTRODUCTION Knowledge regarding the importance of sleep in health and performance and good sleep hygiene practices is low, especially among adolescents and young adults. It is important to improve sleep literacy. Introductory psychology is one of the most highly enrolled courses at colleges and universities. This study tested the impact of an Internet-based learning module on improving sleep literacy in this venue. METHODS An Internet-based supplementary learning module containing sleep physiology and hygiene information was developed using content from the Harvard Medical School sleep educational website http://www.understandingsleep.org. Access to the module was provided as an extra credit activity for 2 of 4 sections (Supplemental Sleep, SS, N = 889) of an introductory college psychology course during their standard instruction on sleep and dreaming. The remaining 2 sections (Standard Instruction, SI, N = 878) only were encouraged to visit the website without further direction. Level of knowledge was assessed before and after availability to the module/website and at the end of the semester. Students were asked to complete a survey at the end of the semester inquiring whether they made any changes in their sleep behaviors. RESULTS Two hundred fifty students participated in the extra credit activity and had data available at all testing points. Students in the SS Group had a significant improvement in sleep knowledge test scores after interacting with the website in comparison to the SI group (19.41 ± 3.15 vs. 17.94 ± 3.08, p < 0.001). This difference persisted, although at a lower level, at the end of the semester. In addition, 55.9% of the SS group versus 45.1% of the SI group indicated that they made changes in their sleep habits after participation in the extra credit sleep activity (p < 0.01). The most common change was a more consistent wake time. CONCLUSION Use of a supplementary internet-based sleep learning module has the potential to enhance sleep literacy and change behavior among students enrolled in an introductory college psychology course.

Dopaminergic agonists differentially affect open-field activity of rats with A10 lesions.

Dopaminergic systems appear to exert considerable control over locomotor activity. Although dopamine neurons are located in relatively close proximity within the mesencephalon, their axons project to more diffuse areas, perhaps reflecting some underlying heterogeneity in their function. The purpose of this study was to determine whether dopamine agonists differentially affect activity by acting upon distinct dopamine systems. Bilateral radio-frequency lesions of area A10 in rats failed to affect spontaneous open-field behavior over a 1-month postoperative period. When injected with 1 mg/kg of apomorphine, however, experimental rats more than doubled their activity as compared to the response of sham-operated controls. In contrast, no difference between the two groups of animals was observed in terms of increased activity following 3 mg/kg of either d-amphetamine or methylphenidate. These results are consistent with previous work indicating the involvement of ventromedial mesencephalic dopamine somata in the control of locomotor activity. The data suggest, however, that systems in addition to the dopaminergic mesolimbic projection are responsible, in part, for the hyperactivity elicited by d-amphetamine or methylphenidate.

Scopolamine administration and NBM lesions differentially affect performance in an operant discrimination task

Effects of cholinergic modulation on differential conditioning performance in rats were evaluated in four experiments. Animals were first trained on an operant discrimination task. In Experiment 1, performance was evaluated following different doses of physostigmine (PHY) or scopolamine (SCO). SCO impaired performance in a dose-dependent manner; doses causing moderate impairment were selected for the remainder of the study. In Experiment 2, to test effects of PHY on SCO-impaired animals, rats were tested with injections of SCO (0.125 mg/kg) plus saline, injections of SCO (0.125 mg/kg) plus PHY (0.03125 mg/kg), or two injections of saline. SCO reduced total responding, but PHY failed to attenuate the effect. Although SCO decreased performance, response patterns suggested that discrimination ability per se was unaffected. In Experiment 3, animals were given bilateral lesions of the nucleus basalis magnocellularis (NBM); performance was reassessed with or without PHY (0.03125 mg/kg) or SCO (0.125 mg/kg). Lesions alone did not affect total responding; but discrimination ability was impaired, as reflected by reduced successes and increased errors. As in Experiment 2, SCO reduced responding without affecting discrimination ability, but PHY did not improve SCO-impaired task performance. In Experiment 4, 12 months after lesions, nondrug performance of animals was reassessed. Control animals showed recovery after one session, whereas lesioned animals took four sessions to show recovery.