Retations of the effectiveness of KX01 Mesylate haloperidol in blocking stress-induced reinstatement because the data suggest it may nonspecifically suppress behavior engendered by a variety of events at that dose. Pharmacological Manipulation (Example 1) Evaluating the effects of a pharmacological agent on prime-, cue- and footshock-induced reinstatement of responding previously reinforced with cocaine Testing the effects of the kappa opioid receptor (KOR) antagonist, JDTic: Figure 3 illustrates the effects of JDTic (vehicle, 3, 10 and 30 mg/kg i.g.), a KOR antagonist, on prime-, cue- and footshock-induced reinstatement of extinguished lever pressing previously reinforced with 0.5 mg/kg/infusion cocaine. Separate groups of 12 rats each were used for each dose condition. The effects of JDTic on prime- and footshock-induced reinstatement had been previously reported (Beardsley et al., 2005) using similar data. Separate nonparametric (Kruskall Wallis) tests were conducted within each reinstatement condition on active lever presses across dosage PubMed ID:http://www.ncbi.nlm.nih.gov/pubmed/21112321 groups for the last session of self-administration and for last session of extinction and were found to not significantly (P<0.05) differ indicating that the rats had been trained to similar levels of cocaine self-administration and extinction prior to reinstatement testing (data not shown). These analyses thus established that rats within each treatment group had been self-administrating cocaine comparably before extinction, and that extinction had comparable effects on responding before testing, enabling their comparisons during reinstatement testing. Separate one-way t-tests were conducted on active lever presses of individual vehicle groups within each reinstatement condition to their respective final sessions of extinction to determine if cocaine primes, cue presentations and footshocks were effective in reinstating responding. In each of the three comparisons, active lever presses significantly (P<0.05) increased during reinstatement tests relative to their immediately preceding extinction session. Mean ( EM) numbers of active lever presses during the last session of extinction emitted by the vehicle treatment group for the prime-, cue- and footshock conditions were 17.67 (?.548), 14.17 (?.426) and 36.75 (?.890), respectively, and increased to 51.67 (?0.96), 54.92 (?.578) and 64.75 (?4.33) during reinstatement testing. These increases were statistically significant (prime: t=3.170, df=11,watermark-text watermark-text watermark-textCurr Protoc Neurosci. Author manuscript; available in PMC 2013 October 01.Beardsley and SheltonPageP=0.0045; cue: t=10.83, df=11, P<0.0001; footshock: t=2.314, df=11, P=0.0205). These significant increases in active lever responding during the reinstatement conditions, relative to their respective final extinction sessions, indicates that the conditions used effectively resulted in reinstatement in the vehicle treated groups for each reinstatement condition. When tested with JDTic, levels of footshock-induced reinstatement were reduced relative to vehicle conditions, significantly so at the 10 and 30 mg/kg conditions (Dunn's Multiple Comparison Tests, p<0.05). Levels of prime- and cue-induced reinstatement were unaffected by JDTic. The selectivity of effects on footshock-induced, but neither on prime- nor cueinduced reinstatement, suggests that the effects on stress-induced reinstatement were likely not attributable to non-specific suppressing effects of JDTic (or all reinstate.