Hooded rats in 4 groups (10 M, 10 F each) were given shuttlebox avoidance training, 25 trials a day for 6 consecutive days, using a compound light-click warning signal and white noise as an aversive unconditioned stimulus at either 90, 100, 110, or 120 db SPL. Avoidance performance was an inverted U-shaped function of noise level. Females were significantly more active than males at each noise level, but although females performed more avoidance responses than males at each level, this sex difference was not significant. Avoidance response latencies were relatively invariant across training sessions for each group, as were escape responses latencies for the 100- and 110-db groups. Escape response latencies for the 90- and 120-db groups increased across training sessions. Shuttlebox performance as a function of increasing white noise UCS level is, in most respects, similar to performance obtained with increasing shock intensities.
Abstract Nicotine, a major psychoactive component of tobacco smoke, alters gamma‐aminobutyric acid (GABA) modulation of dopamine neurons in the ventral tegmental area (VTA). Changes in structural neuroplasticity can occur in GABAergic parvalbumin (PRV) positive neurons, which are enveloped by structures of the extracellular matrix called perineuronal nets (PNNs). In the current study, rats were trained to self‐administer intravenous nicotine (0.03 mg/kg/infusion) for 21 days in 1‐hour daily sessions with an incrementing fixed ratio requirement; a control group received saline infusions. At either 45 minutes or 72 hours after the last session, immunofluorescence measurements for PNNs, PRV and c‐Fos were conducted. In VTA, nicotine self‐administration reduced the number of PRV+ cells surrounded by PNNs at 45 minutes, as well as reducing the intensity of PNNs, suggesting a remodeling of GABA interneurons in this region; the number of PRV+ cells surrounded by PNNs was also reduced at 72 hours. A similar reduction of PNNs occurred in orbitofrontal cortex (OFC) but not in medial prefrontal cortex (prelimbic or infralimbic), 45 minutes after the last session; PNNs were not detected in nucleus accumbens (shell or core). The reduction of PNNs in VTA and OFC was unrelated to c‐Fos + cells, as the percent of wisteria floribunda agglutinin + cells co‐expressing c‐Fos was decreased in OFC but not in VTA. Thus, nicotine self‐administration remodeled PNNs surrounding GABA interneurons in VTA and its indirect connections to OFC, suggesting a new possible molecular target where nicotine‐induced neuroplasticity takes place. PNN manipulations may prevent or reverse the different stages of tobacco addiction.