Changes in hippocampal morphology following chronic treatment with the synthetic cannabinoid WIN 55,212-2.

Learning and memory are often correlated with cellular changes within the hippocampus, and drugs or environmental factors which affect learning and memory will thus often induce observable morphological changes in this structure. Like tetrahydrocannabinol (THC) itself, many synthetic cannabinoids such as the CB-1 receptor agonist WIN 55,212-2 will induce learning and memory changes. In the current study, we investigate whether or not these changes could be related to structural changes within the hippocampus. Adult male Sprague-Dawley rats were injected twice daily (12:00 and 0:00 h) subcutaneously with WIN 55,212-2 (2.0 mg/kg) in DMSO or DMSO for 21 days. On day 22, animals were perfused and stained immunochemically for the dendritic marker MAP-2, or with cresyl violet. Morphometric analysis showed dendritic rearrangement with increased staining of MAP-2 in CA3 and the lower blade of the dentate gyrus. However, a loss of staining was observed in CA1. Counting of cresyl violet stained sections showed an apparent increase in granule cell number in the lower blade of the dentate gyrus. This work shows the potential for cannabinoids to influence hippocampal morphology. The pattern of changes may be similar to that seen after ischemic or toxic damage, but may be opposite to changes seen in stress.

Gonadectomy in adult life increases tyrosine hydroxylase immunoreactivity in the prefrontal cortex and decreases open field activity in male rats.

The prefrontal cortices in rats participate in a range of cognitive, emotional, and locomotor functions that are dependent on its rich catecholamine innervation. Sex differences identified in many of these functions suggest that the prefrontal cortex is also influenced by gonadal hormones. Previous studies have shown that prefrontal catecholamines can be modified by changes in the hormone environment in developing animals. The present analyses, carried out in male rats gonadectomized as adults, with and without supplementation with testosterone proprionate, and examined at intervals from two days to 10 weeks after surgery, revealed that both the anatomical organization of prefrontal catecholamine afferents, and a behavioral measure sensitive to their selective lesioning remain highly responsive to changes in testicular hormones in adulthood. Thus, gonadectomy in adult male rats rapidly led to a large but transient decrease in the density of tyrosine hydroxylase immunoreactivity in all layers of the dorsal anterior cingulate cortex. This was followed by a sustained period in which immunoreactivity in the supragranular layers returned to levels that were just below normal (between 72 and 79% of normal), and labeling in deep laminae stabilized at considerably elevated innervation densities (approximately 150% of normal). Neither the acute decrease nor the chronic over-innervation characteristic of gonadectomized animals was observed in rats that were gonadectomized and supplemented with testosterone proprionate. Open field activity assessed along a corresponding 10 week timeline showed that gonadectomized animals were significantly less active than hormonally intact controls, a behavioral pattern opposite to the hyperactivity which persists following prefrontal dopamine lesions. Gonadectomized animals supplemented with testosterone proprionate, on the other hand, had open field scores that were not significantly different from controls. Taken together, these findings indicate that the adult hormone environment provides a significant, and seemingly functionally significant influence over the catecholamine innervation of the rat prefrontal cortex. Such lifelong responsiveness of the prefrontal cortical catecholamines to circulating hormones suggests that gonadal steroids are an active component of the biology of normal adult cognition, and may also have relevance for cortical dysfunction in disorders such as schizophrenia which are not only strongly tied to the catecholamines, but exhibit considerable biases among men and women as well.

Summer sun exposure: knowledge, attitudes, and behaviors of Midwest adolescents.

BACKGROUND: Extensive print, radio, and television coverage about the dangers of sun exposure and benefits of sun protection occurred over the past decade. Illinois teen knowledge and attitudes about sun exposure/protection, sun-exposure/protection behavior, and information sources were determined by a summer telephone survey. METHODS: Telephone interviews with 658 teenagers between ages 11 and 19 included African-American, Asian, Hispanic, Native American, and white teenagers. RESULTS: Teens knew that too much sun was harmful as it caused skin cancer and sunburn. Sunburn was mentioned more often by those with skin types that burned easily and tanned poorly (I,II) (P < 0.001), was better known to girls than to boys (P < 0.001), and was recognized more by those with higher socioeconomic status (P < 0.001) but was not associated with age. Widely held sun exposure attitudes were socializing with friends and feeling better when outdoors. On weekdays, boys averaged 5.3 hr (SD, 1.65 hr) outside compared with 3.9 hr (SD, 0.75 hr) for girls (P < 0.001). Teenage boys were more likely to obtain occupational sun exposure, and girls sunbathed. Subjects with skin types I and II reported an average of 3.3 sunburns in the past year. During unprotected sun exposure, extensive numbers of teens with moderate-risk skin type experienced at least 1 sunburn per year. Indoor tanning use was more prevalent among older girls and those with skin types I and II. Sunscreen use was associated with water recreational activities (swimming, water sports, and going to the beach) by girls slightly more than by boys (P < 0.001). Hat-wearing was more common among boys than among girls. CONCLUSIONS: Teen knowledge that excessive sun exposure causes skin cancer and sunburns and that wearing sunscreens and hats were sun-protective methods did not enable sun protection that prevented burning. This is particularly troublesome because severe sunburns in youth are associated with an increased risk of melanoma. Existing teen sunscreen use could be broadened by educating teens to use adequate quantities of sunscreen prior to daily sun exposure to prevent painful burns. Messages to teens that emphasize the short-term consequence of painful sunburns because of inadequate protection during outdoor occupational and non-water-related recreational exposure would increase the relevance of the message and may enable behavioral change. Parents and physicians need to be included in messages that are directed to teens and to become part of their education. Parents could ensure an adequate sunscreen supply for daily use by the family, encourage teens not to deliberately tan, and serve as role models for the use of protective clothing.

Galanin receptor antagonists M40 and C7 block galanin-induced feeding.

Two peptide antagonists of the galanin receptor, M40 (galanin[1-13]-Pro-Pro-[Ala-Leu]2-Ala amide) and C7 (galanin[1-13]-spantide amide), significantly inhibited galanin-induced consumption of a palatable wet cookie mash, when microinjected intraventricularly to satiated rats. Antagonists were effective at doses equimolar to or less than the active doses of galanin. Feeding induced by an overnight fast was not significantly different in rats microinjected with saline as compared to M40 or C7, at doses which inhibited galanin-induced feeding. The activity of the chimeric compound, C7, did not appear to be linked to the properties of its C-terminal spantide-like sequence, as C7 did not induce barrel rolling at doses which inhibited galanin-induced feeding. The IC50 for displacement of 125I-[Tyr26]-porcine galanin 1-29 binding in rat hypothalamic membranes was 15 nM for M40, and 0.2 nM for C7, as compared to 0.8 nM for unlabelled porcine galanin(1-29). These two structurally different galanin antagonists, both demonstrating antagonist activity in vivo in awake, behaving rats, provide promising tools for further analyses of the functional activity of galanin in the mammalian brain.

MK-801 prevents brain lesions and delayed-nonmatching-to-sample deficits produced by pyrithiamine-induced encephalopathy in rats.

Rats were trained on a spatial delayed-nonmatching-to-sample (DNMTS) task and assigned by block randomization to one of four treatments: pyrithiamine-induced thiamine deficiency (PTD), PTD with administration of MK-801 after 12 days, control with MK-801 treatment, and control without MK-801. After 15 days of treatment followed by 21 days of recovery, the PTD rats showed significant deficits for DNMTS accuracy at retention intervals (RI) that ranged from 3.0 s to 15.0 s, the RIs that produced 75% accuracy on DNMTS in staircase training, and the rate at which a novel radial arm maze task was learned. The PTD-treated rats had consistent lesions in the thalamus and the mammillary bodies. MK-801 protected rats from both behavioral deficits and brain lesions (assessed quantitatively and qualitatively) that were produced by the PTD treatment.

Delayed-nonmatching-to-sample performance is impaired by extensive, but not by limited, lesions of the thalamus in the rat.

Two experiments were conducted to determine whether lesions affecting limited areas of the thalamus can impair the performance of rats on a spatial delayed-nonmatching-to-sample (DNMTS) task trained before surgery. In Experiment 1, DNMTS was not affected by lesions produced by injecting 5 microliters of 1 mM N-methyl-D-aspartate into either the midline thalamus (n = 16) or bilaterally 1.0 mm from the midline (n = 16). In experiment 2, radio-frequency lesions were made 1.0 mm lateral to the midline at 3 anterior-posterior locations that destroyed the full rostral-caudal extent of the lateral internal medullary lamina (L-IML; n = 8), or at single anterior-posterior locations that destroyed either the anterior (n = 8) or posterior (n = 8) portions of the L-IML site. Although complete L-IML lesions disrupted DNMTS performance to an extent comparable to that of another study (Mair & Lacourse, 1992), lesions that were restricted to either the anterior or posterior portion of the L-IML site had no significant effect on this task.

Advances in the treatment of nonmelanoma skin cancer.

Nonsurgical and nonradiation therapy for nonmelanoma skin cancer is focusing on immunotherapy, recombinant human gene products, localized delivery of radiant energy, photodynamic therapy, and retinoids. Although they are not currently practical for widespread application to nonmelanoma skin cancer, there is good reason to hope for significant therapeutic advances in these areas, which will make successful nonsurgical therapy widely available.