Pakarinen E.D., Moerschbaecher J.M.
Louisiana State University Medical Center, Department of Pharmacology, 1901 Perdido Street, New Orleans, LA 70112-1393, USA.
Behav Pharmacol. 1995 Mar;6(2):156-166.
There is evidence that low doses of convulsant agents may enhance acquisition under various behavioral procedures. The following experiments were undertaken to establish whether the putative GABA(A) antagonist pentylenetetrazole, and known GABA(A) receptor antagonists picrotoxin, picrotoxinin and bicuculine, might also enhance acquisition. Learning was studied under two different schedules of food presentation using the technique of repeated acquisition. Under this procedure, subject were required to acquire a different three-response sequence each session. Sequence completions were reinforced under a fixed-ratio five (FR 5) schedule, which engendered a low level of errors. A chain strained-ratio schedule was also studied because it engendered a high level of errors. Pentylenetetrazole (PTZ) (0.32-32mg/kg) generally produced a dose-related decrease in responding at higher doses (10-32mg/kg), while at lower doses (0.32-5.6mg/kg) response rate was not affected. PTZ generally disrupted accuracy of responding only at doses that decreased the rate of responding. Like PTZ, the noncompetitive GABA(A) receptor antagonist picrotoxin decreased the overall rate of responding and disrupted accuracy only at the higher doses tested (0.13-0.32mg/kg) in three of four subjects. At low doses (0.0032-0.1mg/kg), response rates and accuracy were unaffected when compared to the control ranges. Picrotoxinin, an active metabolite of picrotoxin, increased errors at doses that decreased the overall rate of responding. Conversely, the competitive GABA(A) receptor antagonist bicuculline (0.0032-0.56mg/kg) had no effect on accuracy and only decreased the rate of responding at doses that produced convulsions. Under the chain strained-ratio schedule, PTZ and picrotoxinin failed to enhance acquisition. These data suggest that pentylenetetrazole, picrotoxin, picrotoxinin and bicuculline do not reliably enhance acquisition in the squirrel monkey, and that differences exist between competitive and noncompetitive GABA(A) antagonists with regard to their effects on acquisition processes in the squirrel monkey. d-amphetamine, on the other hand, disrupted acquisition under the fixed-ratio schedule while at certain doses it enhanced acquisition under the strained-ratio schedule. The data also suggest that classical brain stem and cortical stimulants differ in terms of their ability to enhance acquisition under a strained-ratio schedule and that these differences may relate to their effects on conditioned reinforcement.
有证据表明，低剂量的惊厥剂可能会在各种行为程序下增强习得能力。进行了以下实验，以确定假定的GABA(A)拮抗剂戊四氮以及已知的GABA(A)受体拮抗剂印防己毒素、印防己毒素宁和荷包牡丹碱是否也能增强习得能力。使用重复习得技术，在两种不同的食物呈现时间表下研究学习情况。在此程序下，要求受试者在每个实验环节中习得不同的三反应序列。在固定比率为五（FR 5）的时间表下强化序列完成情况，这会导致较低的错误率。还研究了一种连锁应变比率时间表，因为它会导致较高的错误率。戊四氮（PTZ）（0.32 - 32mg/kg）通常在较高剂量（10 - 32mg/kg）时使反应呈剂量相关的减少，而在较低剂量（0.32 - 5.6mg/kg）时反应率不受影响。PTZ通常仅在降低反应率的剂量下干扰反应的准确性。与PTZ一样，非竞争性GABA(A)受体拮抗剂印防己毒素仅在测试的较高剂量（0.13 - 0.32mg/kg）下降低了总体反应率并干扰了准确性，在四个受试者中有三个出现这种情况。在低剂量（0.0032 - 0.1mg/kg）时，与对照范围相比，反应率和准确性不受影响。印防己毒素宁是印防己毒素的活性代谢产物，在降低总体反应率的剂量下增加了错误率。相反，竞争性GABA(A)受体拮抗剂荷包牡丹碱（0.0032 - 0.56mg/kg）对准确性没有影响，仅在产生惊厥的剂量下降低反应率。在连锁应变比率时间表下，PTZ和印防己毒素宁未能增强习得能力。这些数据表明，戊四氮、印防己毒素、印防己毒素宁和荷包牡丹碱不能可靠地增强松鼠猴的习得能力，并且在竞争性和非竞争性GABA(A)拮抗剂对松鼠猴习得过程的影响方面存在差异。另一方面，d - 苯丙胺在固定比率时间表下干扰习得，而在某些剂量下它在应变比率时间表下增强习得。数据还表明，经典的脑干和皮质兴奋剂在增强应变比率时间表下习得的能力方面存在差异，并且这些差异可能与它们对条件强化的影响有关。
