Michael Vigorito

Fat appetite in rats: the response of infant and adult rats to nutritive and non-nutritive oil emulsions.

Fat appetite was studied in rats using corn oil and mineral oil emulsions. In Experiment 1 ingestive responses to intraoral infusions were measured in rat pups 6-15 days of age. By 12-15 days of age pups responded more to oil emulsions (10% and 30%) than they did to water or emulsifier solution. The corn and mineral oil emulsions were almost as effective as milk but less effective than sucrose (0.3M) in stimulating ingestion. Experiments 2 and 3 examined the acceptance and preference for oil emulsions in adult rats. The corn oil and mineral oil emulsions were equally acceptable to non-deprived rats, as measured by 3-min and 30-min one-bottle tests. Food deprivation increased the one-bottle intake of both emulsions. In two-bottle tests, rats displayed a slight corn oil preference when non-deprived, but developed a strong preference when food deprived. Taken together, the results suggest that rats have an unlearned attraction to the orosensory qualities of emulsified oils and they learn to prefer corn oil based on its postingestive nutritive effects.

The HIV-1 transgenic rat as a model for HIV-1 infected individuals on HAART

HIV-1 viral replication is limited in patients given highly active anti-retroviral therapy (HAART); however, HIV-1 viral proteins are still present. We demonstrate that the developing HIV-1Tg rat, which expresses all of the HIV-1 viral genes except the gag-pol replication genes, maintains lower body weight compared with the F344 control rat. Although HIV-1Tg rats eat and drink less than the control animals, they are not anorexic and show no evidence of anhedonia. At 19 months (mo) of age, HIV-1Tg rats begin to show clinical signs of wasting that progress to death. Using real-time RT-PCR, we compared the expression of the HIV viral proteins Tat, gp120, nef, and vif, in the HIV-1Tg rats at 2-3 mo of age with those at 10-11 mo of age. RNA levels of viral protein in the spleens of younger rats were significantly greater than those in the older rats (P<0.01). Conversely, viral protein mRNA levels in the spinal cord, cerebellum, and striatum were significantly greater in the older rats than in the younger animals (P<0.01). In the prefrontal cortex, Tat and nef expression was significantly greater at 2-3 mo of age than at 10-11 mo of age (P<0.05). These findings indicate that there may be age-dependent differential expression of various HIV viral proteins, with a switch from peripheral immune organs to the CNS, even when the animals are still pre-symptomatic. Our study also demonstrates that this non-infectious rat can be a useful model simulating HIV-1 infected individuals that are on HAART.

Spatial learning and memory in HIV-1 transgenic rats.

HIV-1 infection of the central nervous system impairs neural, cognitive, and behavioral functioning in patients despite antiretroviral therapy. However, studying mechanisms underlying HIV-1-related neurological and cognitive dysfunction has been limited without an adequate animal model. A novel, noninfectious HIV-1 transgenic (HIV-1Tg) rat model was recently created that expresses an HIV-1 provirus with a deletion of functional gag and pol genes. This HIV-1Tg rat reportedly develops clinical manifestations of human HIV disease and thus appears to mimic the persistent infection that results from the presence of HIV viral proteins in the host. We evaluated the HIV-1Tg rat model using the Morris water maze, a popular paradigm for testing learning and memory deficits in rodents. Because of congenital cataracts in HIV-1Tg rats, however, the traditional use of visual navigational cues in this paradigm were precluded. We first designed a modified Morris water maze and demonstrated that neurologically intact rats can effectively learn the water maze in the absence of visual cues and in the presence of non-visual navigation cues. We then tested HIV-1Tg rats in this modified Morris water maze. These HIV-1Tg rats showed a deficit in learning how to swim to the location of the hidden platform but did not show a deficit in their memory of the general location of the hidden platform. These results suggest that the noninfectious HIV-1Tg rat can be a valid model for the behavioral studies of HIV-related neurological dysfunction.

Sex differences in polysaccharide and sugar preferences in rats

The preferences of adult male and female rats for sucrose and polysaccharide (Polycose) solutions were measured in three experiments. In Experiment 1, male and female rats did not differ in their preference for molar solutions of sucrose or Polycose as measured by 24-hr solution vs. water tests. In Experiment 2, however, male rats displayed a greater preference for Polycose, and females a greater preference for sucrose as measured in 3-min and 30-min/day sucrose vs. Polycose tests. Both sexes preferred Polycose to sucrose at low concentrations, but switched their preference at higher concentrations. Experiment 3 revealed that both male and female rats strongly preferred 32% sucrose to 32% Polycose in 30-min/day two-solution tests, but this preference did not persist when the rats were given 24-hr/day access to the two solutions. Male rats lost their sucrose preference, while female rats developed a preference for Polycose over sucrose. The sexes also differed in that the female rats increased their total caloric intake more and consumed proportionately more carbohydrate than did the male rats during the 24-hr/day test. The findings demonstrate that while both male and female rats have an avid appetite for polysaccharide and sucrose solutions, they differ in their short-term and long-term relative preferences for the two carbohydrates, as well as in their caloric and diet selection responses to the carbohydrate solutions. The possible functional significance of these sex differences are discussed.

Effects of gustatory deafferentation on Polycose and sucrose appetite in the rat.

Recent studies have revealed that rats are strongly attracted to the taste of starch-derived polysaccharides, and suggest that the taste receptors involved differ from those that respond to sucrose. The present study examined the possibility that different gustatory nerves mediate the rats taste and appetite for polysaccharides and sucrose. This was accomplished by measuring the effects of selective gustatory nerve transection on the intake of Polycose and sucrose solutions in nondeprived female rats. Bilateral transection of the chorda tympani nerve produced comparable reductions in Polycose and sucrose intake, but bilateral transection of the glossopharyngeal nerve selectively reduced the intake of Polycose. Bilateral transection of the greater superficial petrosal nerve, and to a lesser degree, the pharyngeal branch of the vagus nerve, increased sucrose intake without affecting Polycose intake. These results indicate that while no single gustatory nerve mediates sucrose or polysaccharide taste, there is some specialization of function within the peripheral gustatory system. Combined bilateral transections of all four gustatory nerves produced the greatest reduction in solution intake, and reduced Polycose and sucrose consumption to the same degree. The suppressive effect was only partial, however, which indicates that relatively few intact taste receptors are required to maintain the rats appetite for sugar and polysaccharide solutions.

The HIV-1 transgenic rat model of neuroHIV

Despite the ability of current combination anti-retroviral therapy (cART) to limit the progression of HIV-1 to AIDS, HIV-positive individuals continue to experience neuroHIV in the form of HIV-associated neurological disorders (HAND), which can range from subtle to substantial neurocognitive impairment. NeuroHIV may also influence substance use, abuse, and dependence in HIV-positive individuals. Because of the nature of the virus, variables such as mental health co-morbidities make it difficult to study the interaction between HIV and substance abuse in human populations. Several rodent models have been developed in an attempt to study the transmission and pathogenesis of the HIV-1 virus. The HIV-1 transgenic (HIV-1Tg) rat is a reliable model of neuroHIV because it mimics the condition of HIV-infected patients on cART. Research using this model supports the hypothesis that the presence of HIV-1 viral proteins in the central nervous system increases the sensitivity and susceptibility of HIV-positive individuals to substance abuse.

Classically conditioned tail flexion in rats: CR-contingent modification of US intensity as a test of the preparatory response hypothesis

A classically conditioned tail flexion in rats with a white noise as the conditioned stimulus and a tailshock as the unconditioned stimulus is shown to arise as a result of contingent presentation of the two stimuli rather than from sensitization or pseudoconditioning. After achieving an asymptote for conditioned tail flexion, different groups received response-contingent tail-shock increment, decrement, or omission. None of these treatments appreciably altered the probability of a conditioned response. Evidence is presented demonstrating that the response was sensitive to changes in the relationship between the stimuli and that the subjects could differentiate the various shock levels. The present data are viewed as inconsistent with the preparatory response hypothesis, which posits that classically conditioned behavior depends upon intrinsic reinforcement of components of the conditioned response syndrome. The possibility is discussed that classically conditioned responses observed in the laboratory are often only part of a larger, perhaps more clearly instrumental, set of behaviors that would occur in the unrestrained animal.

Effects of SOA and saccharin adulteration on polycose preference in rats

Female rats were tested for their preference for a 32% Polycose solution, and for 32% Polycose solutions made bitter or sweet by adulteration with either 0.05% sucrose octa acetate (SOA) or 0.2% saccharin during 24 hr/day two-bottle tests. The rats preferred the saccharin-Polycose to the Polycose, the Polycose to the SOA-Polycose, and strongly preferred the saccharin-Polycose to the SOA-Polycose solution. Additional rats that were given only a Polycose or an SOA-polycose solution, in addition to chow and water, consumed similar amounts of solution, and consumed as much as did the rats given the saccharin-Polycose solution. Thus, while SOA adulteration reduces, and saccharin adulteration increases, the relative palatability of Polycose, they do not alter the animals intake when only one solution is available. In a second experiment rats were given the choice between a 32% Polycose solution and pure Polycose powder, between an SOA-Polycose solution and Polycose powder, or between an SOA-Polycose solution and sucrose powder during both 30-min/day and 24-hr/day preference tests. During the initial short-term test the rats preferred the Polycose solution and, to a lesser degree, the SOA-Polycose solution to the Polycose powder, but they strongly preferred the sucrose powder to the SOA-Polycose solution. During the subsequent long-term test, however, the rats developed a preference for the SOA-Polycose solution over the sucrose powder. The mechanism responsible for this preference switch is not certain, but it may be related to the postingestive effects of the solution, and may also be responsible for the rats hyperphagic response to carbohydrates in solution form but not in powder form.

Conditioned suppression tests of the context-blocking hypothesis: testing in the absence of the preconditioned context.

Two experiments are reported that use rats in a conditioned suppression situation. The experiments, designed to remove confounds that have complicated interpretations of prior research, tested the context-blocking hypothesis, the proposition that static apparatus cues or conditioning contexts can block conditioning to discrete conditioned stimuli (CSs). Experiment 1, like previous work, tested for conditioning to the target CS in the same context that had been preconditioned and in which target conditioning had occurred; the experiment demonstrated a context-blocking like effect. Experiment 2 tested for conditioning not only in the preconditioned context but also in a nonpreconditioned context. Evidence for context blocking appeared similar in the two test situations. This suggests that conditioned contexts block the acquisition of associative strength by discrete CSs at the time of target conditioning (e.g., Rescorla & Wagner, 1972) and not through performance factors at the time of testing (e.g., Gibbon & Balsam, 1981).

Methamphetamine-Induced Behavioral and Physiological Effects in Adolescent and Adult HIV-1 Transgenic Rats

We recently reported that six consecutive days of treatment with a moderate dose of methamphetamine (METH) induced greater behavioral sensitization in adult HIV-1 transgenic (HIV-1 Tg) rats than in adult Fischer 344/NHsd (F344) non-transgenic, wild-type control animals. In the present study, we evaluated the effects of a moderate dose of METH on the brains of adolescent versus adult HIV-1 Tg male rats using both behavioral (METH-induced, stereotypic head movement) and physiological (rectal body temperature) parameters. We found that both the acute and behavior-sensitizing effects of METH were greater in HIV-1 Tg rats compared with controls and also in adolescent rats compared with adult animals, regardless of HIV-1 status. We determined that acute hyperthermic effects of METH as well as tolerance to METH-induced hyperthermia were greater in HIV-1 Tg rats than in controls. Taken together, these results suggest that both the neuroadaptations seen in HIV infection and the immaturity of the adolescent brain are associated with increased sensitivity to the psychoactive and behavior-sensitizing properties of METH. Thus, HIV-infected individuals and adolescents may be more vulnerable to the development of METH abuse and dependence than non-infected individuals and adults.