Habituation, latent inhibition, and extinction.

In two conditioned suppression experiments with a latent inhibition (LI) design, we measured the habituation of rats in preexposure, their LI during conditioning, and then extinction over days. In the first experiment, lick suppression, the preexposed group (PE) showed a significant initial unconditioned response (UR) to the target stimulus and significant long-term habituation (LTH) of that response over days. The significant difference between the PE and nonpreexposed (NPE) groups on the first conditioning trial was due solely to the difference in their URs to the conditioned stimulus (CS)-a habituated response (PE) and an unhabituated response (NPE). In the second experiment, bar-press suppression, little UR to the target stimulus was apparent during preexposure, and no detectable LTH. Thus, there was no difference between the PE and NPE groups on the first conditioning trial. Whether the UR to the CS confounds the interpretation of LI (Exp. 1) or not (Exp. 2) can only be known if the UR is measured. In both experiments, LI was observed in acquisition. Also in both experiments, rats that were preexposed and then conditioned to asymptote were significantly more resistant to extinction than were the rats not preexposed. This result contrasts with the consistently reported finding that preexposure either produces less resistance to extinction or has no effect on extinction. The effect of stimulus preexposure survived conditioning to asymptote and was reflected directly in extinction. These two experiments provide a cautionary procedural note for LI experiments and have shown an unexpected extinction effect that may provide new insights into the interpretation of LI.

Chronic anabolic androgenic steroid exposure alters corticotropin releasing factor expression and anxiety-like behaviors in the female mouse.

In the past several decades, the therapeutic use of anabolic androgenic steroids (AAS) has been overshadowed by illicit use of these drugs by elite athletes and a growing number of adolescents to enhance performance and body image. As with adults, AAS use by adolescents is associated with a range of behavioral effects, including increased anxiety and altered responses to stress. It has been suggested that adolescents, especially adolescent females, may be particularly susceptible to the effects of these steroids, but few experiments in animal models have been performed to test this assertion. Here we show that chronic exposure of adolescent female mice to a mixture of three commonly abused AAS (testosterone cypionate, nandrolone decanoate and methandrostenolone; 7.5 mg/kg/day for 5 days) significantly enhanced anxiety-like behavior as assessed by the acoustic startle response (ASR), but did not augment the fear-potentiated startle response (FPS) or alter sensorimotor gating as assessed by prepulse inhibition of the acoustic startle response (PPI). AAS treatment also significantly increased the levels of corticotropin releasing factor (CRF) mRNA and somal-associated CRF immunoreactivity in the central nucleus of the amygdala (CeA), as well as neuropil-associated immunoreactivity in the dorsal aspect of the anterolateral division of the bed nucleus of the stria terminalis (dBnST). AAS treatment did not alter CRF receptor 1 or 2 mRNA in either the CeA or the dBnST; CRF immunoreactivity in the ventral BnST, the paraventricular nucleus (PVN) or the median eminence (ME); or peripheral levels of corticosterone. These results suggest that chronic AAS treatment of adolescent female mice may enhance generalized anxiety, but not sensorimotor gating or learned fear, via a mechanism that involves increased CRF-mediated signaling from CeA neurons projecting to the dBnST.

Electrolytic, but not neurotoxic, lesions to the lateral tegmental tract increase acoustic startle amplitude and reduce startle stimulus-induced freezing.

Startle amplitude and startle stimulus-induced freezing (an index of fear) were measured in a standard acoustic startle response (ASR) paradigm in male Sprague-Dawley rats. Groups with electrolytic lesions to the lateral tegmental tract (LTG) or with axon-sparing lesions to the area around LTG made with the neurotoxin NMDA were compared with vehicle-injected or sham operated control groups on these response measures. Replicating previous results (Leaton & Brucato, 2001), electrolytic lesions to LTG significantly reduced freezing and produced a persistent 300% increase in ASR amplitude compared with all other groups. The NMDA lesions had no effect on freezing or on ASR amplitude compared with the controls. In additional testing the rats with electrolytic lesions to LTG did not differ from controls in the acquisition or retention of context freezing using a footshock unconditioned stimulus. The data made a small, but necessary, step in further clarifying two pathways that modify ASR. The source of the descending pathway that provides tonic inhibition of the sensory input to the ASR circuitry is not within the LTG. The ascending pathway that carries the fear-inducing dimensions of the acoustic stimulus to the amygdala by way of the medial geniculate nucleus does not have an intermediate synapse in the area within LTG.

The effect of amygdala lesions on conditional and unconditional vocalizations in rats.

Electrolytic lesions centered on the amygdaloid central nucleus (ACe) resulted in the inability of rats to acquire a Pavlovian conditional vocalization response. Conditioning consisted of pairing a light conditional stimulus with a tailshock unconditional stimulus (US). The thresholds of three unconditional responses (URs) to tailshock were assessed prior to conditioning. These URs are organized at spinal (spinal motor reflexes), medullary (vocalizations during shock), and forebrain (vocalization afterdischarges, VADs) levels of the neuraxis. Compared to sham-lesioned controls, rats with amygdala lesions exhibited a selective elevation in the threshold of VADs. During conditioning the amplitude and duration of VADs were selectively reduced in amygdala-lesioned rats. These findings support earlier observations of that elicitation of VADs by tailshock correlates with the capacity of this US to support fear conditioning. The ACe may be involved in both associative and non-associative aspects of fear conditioning, but for progress in our understanding it is essential to evaluate its role in the generation of conditioning relevant URs.