Baclofen alters gustatory discrimination capabilities and induces a conditioned taste aversion (CTA)

<p>Abstract</p> <p>Background</p> <p>Studies intending to measure drug-induced changes in learning and memory are challenged to parse out the effects of drugs on sensory, motor, and associative systems in the brain. In the context of conditioned taste aversion (CTA), drugs that alter the sensorium of subjects and affect their ability to taste and/or feel malaise may limit the ability of investigators to make conclusions about associative effects of these substances. Since the GABAergic system is implicated in inhibition, the authors were hopeful to use the GABA agonist, baclofen (BAC), to enhance extinction of a CTA, but first a preliminary evaluation of BAC's peripheral effects on animals' sensorium had to be completed due to a lack of published literature in this area.</p> <p>Findings</p> <p>Our first experiment aimed to evaluate the extent to which the GABA_Bagonist, BAC, altered the ability of rats to differentiate between 0.3% and 0.6% saccharin (SAC) in a two bottle preference test. Here we report that 2 or 3 mg/kg (i.p.) BAC, but not 1 mg/kg BAC, impaired animals' gustatory discrimination abilities in this task. Furthermore, when SAC consumption was preceded by 2 or 3 mg/kg (i.p.) BAC, rats depressed their subsequent SAC drinking.</p> <p>A second experiment evaluated if the suppression of SAC and water drinking (revealed in Experiment 1) was mediated by amnesiac effects of BAC or whether BAC possessed US properties in the context of the CTA paradigm. The time necessary to reach an asymptotic level of CTA extinction was not significantly different in those animals that received the 3 mg/kg dose of BAC compared to more conventionally SAC + lithium chloride (LiCl, 81 mg/kg) conditioned animals.</p> <p>Conclusions</p> <p>Our findings were not consistent with a simple amnesia-of-neophobia explanation. Instead, results indicated that 2 and 3 mg/kg (i.p.) BAC were capable of inducing a CTA, which was extinguishable via repeated presentations of SAC only. Our data indicate that, depending on the dose, BAC can alter SAC taste discrimination and act as a potent US in the context of a CTA paradigm.</p

Long-term age-dependent behavioral changes following a single episode of fetal N-methyl-D-Aspartate (NMDA) receptor blockade

BACKGROUND: Administration of the N-methyl-D-aspartate (NMDA) antagonist ketamine during the perinatal period can produce a variety of behavioral and neuroanatomical changes. Our laboratory has reported reliable changes in learning and memory following a single dose of ketamine administered late in gestation. However, the nature of the drug-induced changes depends on the point during embryonic development when ketamine is administered. Embryonic day 18 (E18) rat fetuses pre-treated with ketamine (100 mg/kg, i.p. through the maternal circulation) and taught a conditioned taste aversion (CTA) learn and remember the CTA, whereas E19 fetuses do not. The current study sought to determine if long-term behavioral effects could be detected in animals that received ketamine or a saline control injection on either E18 or E19. Rat behavior was evaluated on two different measures: spontaneous locomotion and water maze learning. Measurements were collected during 2 periods: Juvenile test period [pre-pubertal locomotor test: Postnatal Day 11 (P11); pre-pubertal water maze test: P18] or Young-adult test period [post-pubertal locomotor test: P60; post-pubertal water maze test: P81]. RESULTS: Water maze performance of ketamine-treated rats was similar to that of controls when tested on P18. Likewise, the age of the animal at the time of ketamine/saline treatment did not influence learning of the maze. However, the young-adult water maze test (P81) revealed reliable benefits of prenatal ketamine exposure – especially during the initial re-training trial. On the first trial of the young adult test, rats treated with ketamine on E18 reached the hidden platform faster than any other group – including rats treated with ketamine on E19. Swim speeds of experimental and control rats were not significantly different. Spontaneous horizontal locomotion measured during juvenile testing indicated that ketamine-treated rats were less active than controls. However, later in development, rats treated with ketamine on E18 were more active than rats that received the drug on E19. CONCLUSION: These data suggest that both the day in fetal development when ketamine is administered and the timing of post-natal behavioral testing interact to influence behavioral outcomes. The data also indicate that the paradoxical age-dependent effects of early ketamine treatment on learning, previously described in fetuses and neonates, may also be detected later in young adult rats

Enhanced Extinction of Aversive Memories by High-Frequency Stimulation of the Rat Infralimbic Cortex

Electrical stimulation of the rodent medial prefrontal cortex (mPFC), including the infralimbic cortex (IL), immediately prior to or during fear extinction training facilitates extinction memory. Here we examined the effects of high-frequency stimulation (HFS) of the rat IL either prior to conditioning or following retrieval of the conditioned memory, on extinction of Pavlovian fear and conditioned taste aversion (CTA). IL-HFS applied immediately after fear memory retrieval, but not three hours after retrieval or prior to conditioning, subsequently reduced freezing during fear extinction. Similarly, IL-HFS given immediately, but not three hours after, retrieval of a CTA memory reduced aversion during extinction. These data indicate that HFS of the IL may be an effective method for reducing both learned fear and learned aversion